Choose Your Country or Region

Raltegravir (MK-0518)

Name: Raltegravir (MK-0518)
Brand: Selleck Chemicals
SKU: S2005
Rating: 5 (54 reviews)

Catalog No.S2005

For research use only.

Raltegravir (MK-0518) is a potent integrase (IN) inhibitor for WT and S217Q PFV IN with IC50 of 90 nM and 40 nM in cell-free assays, respectively. It shows greater than 1000-fold selectivity for HIV-1 IN over several related Mg2+-dependent enzyme such as HCV polymerase, HIV reverse transcriptase, HIV RNaseH and human α-, β-, γ-polymerases.

Raltegravir (MK-0518) Chemical Structure

CAS No. 518048-05-0

Selleck's Raltegravir (MK-0518) has been cited by 54 publications

Purity & Quality Control

Choose Selective Integrase Inhibitors

Related Compound Libraries

Other Integrase Products

Cabotegravir (GSK1265744)^New

Cabotegravir (GSK744, GSK1265744, S/GSK1265744) is a long-acting HIV integrase inhibitor against a broad range of HIV subtypes, and inhibits the HIV-1 integrase catalyzed strand transfer reaction with IC50 of 3.0 nM. Phase 2.
Tenofovir Alafenamide (GS-7340)^New

Tenofovir Alafenamide (GS-7340) is a prodrug of tenofovir, which is a reverse transcriptase inhibitor, used to treat HIV and Hepatitis B.
Elvitegravir (JTK-303)

Elvitegravir (GS-9137, JTK-303) is an HIV integrase inhibitor for HIV-1 IIIB, HIV-2 EHO and HIV-2 ROD with IC50 of 0.7 nM, 2.8 nM and 1.4 nM in cell-free assays, respectively.
BMS-707035

BMS-707035 is a specific HIV-I integrase (IN) inhibitor with IC50 of 15 nM. Phase 2.
Dolutegravir (GSK1349572)

Dolutegravir (GSK1349572, S/GSK1349572) is a two-metal-binding HIV integrase inhibitor with IC50 of 2.7 nM in a cell-free assay, modest activity against raltegravir-resistant signature mutants Y143R, Q148K, N155H, and G140S/Q148H.
MK-2048

MK-2048 is a potent inhibitor of integrase (IN) and IN_R263K with IC50 of 2.6 nM and 1.5 nM, respectively.
Maraviroc (UK-427857)

Maraviroc (UK-427857) is a CCR5 antagonist for MIP-1α, MIP-1β and RANTES with IC50 of 3.3 nM, 7.2 nM and 5.2 nM in cell-free assays, respectively. Maraviroc is used in the treatment of HIV infection.
Tenofovir (GS 1278) Disoproxil Fumarate

Tenofovir Disoproxil Fumarate (GS-1278, Tenofovir DF) belongs to a class of antiretroviral drugs, it inhibits the activity of HIV reverse transcriptase by competing with the natural substrate deoxyadenosine 5’-triphosphate and, after incorporation into DNA, by DNA chain termination.
Zidovudine

Zidovudine (ZDV, Azidothymidine, NSC 602670,Retrovir) is a nucleoside analogue reverse transcriptase inhibitor, used to treat HIV. It could decrease the HDR efficiency and decrease CRISPR-mediated sequence-specific genome knockin events while increaseing knockout efficiency.

Download Inhibitor Catalog

Integrase Signaling Pathway Map

Biological Activity

Description

Features

The 1st approved human immunodeficiency virus type 1 (HIV-1) integrase inhibitor.

Targets

Integrase (S217Q PFV) ^[1] (Cell-free assay)	Integrase (WT PFV) ^[1] (Cell-free assay)
40 nM	90 nM

In vitro

PFV IN carrying the S217H substitution is 10-fold less susceptible to Raltegravir with IC50 of 900 nM. PFV IN displays 10% of WT activity and is inhibited by Raltegravir with an IC50 of 200 nM, indicating a ~twofold decrease in susceptibility to the IN strand transfer inhibitor (INSTI) compared with WT IN. S217Q PFV IN is as sensitive to Raltegravir as the WT enzyme. ^[1] Raltegravir is metabolized by glucuronidation, not hepatically. Raltegravir has potent in vitro activity against HIV-1, with a 95% inhibitory concentration of 31?0 nM, in human T lymphoid cell cultures. Raltegravir is also active against HIV-2 when Raltegravir is tested in CEMx174 cells, with an IC95 of 6 nM. Raltegravir metabolism occurs primarily through glucuronidation. Drugs that are strong inducers of the glucuronidation enzyme, UGT1A1, significantly reduce Raltegravir concentrations and should not be used. Raltegravir exhibits weak inhibitory effects on hepatic cytochrome P450 activity. Raltegravir does not induce CYP3A4 RNA expression or CYP3A4-dependent testosterone 6-β-hydroxylase activity. ^[2] Raltegravir cellular permeativity is reduced in the presence of magnesium and calcium. ^[3] Raltegravir and related HIV-1 integrase (IN) strand transfer inhibitors (INSTIs efficiently block viral replication. ^[4] In acutely infected human lymphoid CD4+ T-cell lines MT-4 and CEMx174, SIVmac251 replication is efficiently inhibited by Raltegravir, which shows an EC90 in the low nanomolar range. ^[5]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

MT4	NGf4O4hCdnSrdnnyZYwh[XO\|YYm=			MXfBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDIeY1idiCrbX31co9l\W[rY3nlcoN6KH[rcoXzJFEhO0JiaX7m[YN1\WRiaX6gbJVu[W5iTWS0JINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZidnnyZYwhemWybHnjZZRqd25uIFXDOVAhRSByLkCwNVQh\|ryPLh?=	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDV2MUeyOkc,OTh3NEG3NlY9N2F-
MT-4	NI\lOI1CdnSrdnnyZYwh[XO\|YYm=			M4\seWFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGh2dWGwIHntcZVvd2SnZnnjbYVv[3lidnnyeZMhOSB\|QjDpcoZm[3SnZDDpckBpfW2jbjDNWE01KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[geolz[WxicnXwcIlk[XSrb36sJGVEPTBiPTCwMlAxOThizszNMi=>	MkTXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThzNkC1NlEoRjF6MU[wOVIyRC:jPh?=
MT-4	M4O2[2FvfGm4aYLhcEBie3OjeR?=			NHS1SFZCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEB3\XOrY4XsZZIhe3SxbXH0bZRqeyC4aYL1d{BINXC\|ZYXkc5R6eGWmIFj1cYFvKGmvbYXuc4Rm\mmlaXXuZ5khfmm{dYOgbY5n\WO2ZXSgbY4hcHWvYX6gUXQuPCClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJJZqemGuIILldIxq[2G2aX;uMEBGSzVyIE2gNE4xODJizszNMi=>	MlXJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThzNkC1NlEoRjF6MU[wOVIyRC:jPh?=
MT2	MniyRY51cX[rcnHsJIF{e2G7		NHfKWZg{KHSxIESg[IF6ew>?	NH;ZdGxCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZzIF7MOE0{KGmwZnXjeIVlKGmwIHj1cYFvKE2WMjDj[YxteyCvZXHzeZJm\CCjZoTldkA{KHSxIESg[IF6eyCkeTDseYNq\mW{YYPlJJJmeG:{dHXyJIdmdmViYYPzZZktKEWFNUCgQUAxNjByMjFOwG0v	M1T3cVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzN{MEixNFExLz5\|MkC4NVAyODxxYU6=
MT-2	M{jRN2FvfGm4aYLhcEBie3OjeR?=			Ml\jRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOSB\|QjDpcoZm[3SnZDDpckBpfW2jbjDNWE0zKGOnbHzzJIJ6KHS5bzDmc4xlKGSrbIX0bY9vKG2ndHjv[EBqdiCycnXz[Y5k\SCxZjCxNEUhTkKVLDDFR\|UxKD1iMD6wNFMh\|ryPLh?=	MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTFyNECxNEc,OTlzMESwNVA9N2F-
MT2	NV[zV4J6SW62aY\pdoFtKGG\|c3H5		NVfFUVI5PSCmYYnz	M4DMUmFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXjFiM1KgbY5n\WO2ZXSgbY4hcHWvYX6gUXQzKGOnbHzzJIFnfGW{IEWg[IF6eyCkeTDjbIVucWy3bXnu[ZNk\W6lZTDpckBxemW\|ZX7j[UBw\iCoZYThcEBjd3[rbnWgd4VzfW1uIFXDOVAhRSByLkCwOEDPxE1w	NH64NoE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUK4OVM5QSd-MUmyPFU{QDl:L3G+
HOS	MonNRY51cX[rcnHsJIF{e2G7			Mof0RY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOSCqYYLic5Jqdmdid3ns[E11gXCnIHnueIVoemG\|ZTDpcoZm[3SnZDDpckBpfW2jbjDIU3Mh[2WubIOsJGVEPTBiPTCwMlAxPCEQvF2u	M2\pXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzNEmzNFY3Lz5{MUS5N\|A3PjxxYU6=
HOS	MnPPRY51cX[rcnHsJIF{e2G7		MUSzJIhzew>?	MUXBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDD3bYxlNXS7cHWgTJVu[W5iaX3teY5w\GWoaXPp[Y5kgSC4aYL1d{AyKGmwZnXjeIVlKGmwIFjPV{Bk\WyuczDwdoVqdmO3YnH0[YQh\m:{IEOgbJJ{KG[xbHzve4VlKGK7II\pdoFtKGmwZnXjeIlwdiCvZXHzeZJm\CCjZoTldkA1QCCqcoOgZpkhdHWlaX\ldoF{\SC{ZYDvdpRmeiCpZX7lJIF{e2G7LDDFR\|UxKD1iMD6wNFQh\|ryPLh?=	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR5MUixOkc,OjR2N{G4NVY9N2F-
MT2	M2fiXGFvfGm4aYLhcEBie3OjeR?=		NXPvTVlFPSCmYYnz	Mk\DRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOSB\|QjDpckBOXDJiY3XscJMh[W[2ZYKgOUBl[Xm\|LDDFR\|UxKD1iMD6wNFYh\|ryPLh?=	NFvKVHI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEKwO\|M6QCd-MUiyNFc{QTh:L3G+
MT-4	MmPpRY51cX[rcnHsJIF{e2G7			MmqzRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXKDFiUlnOJIhiemKxcnnu[{BqdnSnZ4Lhd4Uh\2WwZTDpcoZm[3SnZDDpckBOXC12IHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4Yhfmm{dYOtbY5lfWOnZDDjfZRweGG2aHnjJIVn\mWldDDifUBOXFRiYYPzZZktKEWFNUCgQUAxNjByNjFOwG0v	MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDN5OEexN{c,OTh\|N{i3NVM9N2F-
MT4	M4q0TWFvfGm4aYLhcEBie3OjeR?=			M4nLdmFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXjFiM1KgbY5n\WO2ZXSgbY4hcHWvYX6gUXQ1KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[geolzfXNvaX7keYNm\CCleYTvdIF1cGmlIHXm[oVkfCCkeTDNWHQh[XO\|YYmsJGVEPTBiPTCwMlAxPiEQvF2u	M{Xqc\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUCwO\|E5Lz5{NEmwNFcyQDxxYU6=
MT4	MnjZRY51cX[rcnHsJIF{e2G7			MVHBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYuOSB\|QjDpcoZm[3SnZDDpckBpfW2jbjDNWFQh[2WubIOgZZN{\XO\|ZXSgZZMheHKxdHXjeIlwdiCjZ3HpcpN1KH[rcoXzMYlv\HWlZXSgZ5l1d3CjdHjpZ{Bm\m[nY4SgZpkhVVSWIHHzd4F6NCCHQ{WwJF0hOC5yME[g{txONg>?	M3;JelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2N{mzN\|YxLz5{NEe5N\|M3ODxxYU6=
MT4	NXjZRodqSW62aY\pdoFtKGG\|c3H5			NFzEWYJCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJfW2jbjDpcY12dm:mZX\pZ4lmdmO7II\pdpV{KDFiM1KgbY5n\WO2ZXSgbY4hcHWvYX6gUXQ1KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[geolzfXNiaX7keYNm\CCleYTvdIF1cGmlIHXm[oVkfCxiRVO1NEA:KDBwMEC2NUDPxE1w	M{HEOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJyNEe5NlA3Lz5{MES3PVIxPjxxYU6=
MT4	NXL0R\|E2TnWwY4Tpc44h[XO\|YYm=		MXOxJIhz	M1PWPGlvcGmkaYTpc44hd2Zid3ns[EB1gXCnIFjJWlEhO0JiaX7m[YN1\WRiaX6gbJVu[W5iTWS0JINmdGy\|IIXzbY5oKGOnbHzzJJBz\S2rbnP1ZoF1\WRid3n0bEBkd22yb4Xu[EBnd3JiMTDodkBu\WG\|dYLl[EA1KGSjeYOgdI9{fCC4aYLhcEBqdm[nY4Tpc44h[nliTWTUJIF{e2G7LDDJR\|UxKD1iMD6wNFYzKM7:TT6=	Mlu5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ7NkOxN\|UoRjJ{OU[zNVM2RC:jPh?=
MT4	NU[4d3diSW62aY\pdoFtKGG\|c3H5			M{fKXWFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXjFiM1KgbY5n\WO2ZXSgbY4hcHWvYX6gUXQ1KGOnbHzzJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCxZjD2bZJ2ey2rbnT1Z4VlKGO7dH;wZZRpd2enbnnjbZR6KGK7IF3UWEBie3OjeTygSWM2OCB;IECuNFA3PCEQvF2u	NIHnNJY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUS0O\|YzOSd-MUm0OFc3OjF:L3G+
MT-4	Mlz4RY51cX[rcnHsJIF{e2G7			MUDBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYhOSCQTESuN{Bp[XKkb4LpcochcW62ZXfyZZNmKEx5NF2gcZV1[W62IHnu[oVkfGWmIHnuJIh2dWGwIF3UMVQh[2WubIOgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjD2bZJ2ey2rbnT1Z4VlKGO7dH;wZZRpcWNiZX\m[YN1KGK7IF3UWEBie3OjeTygSWM2OCB;IECuNFA4KM7:TT6=	NUS0eY93RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUizO\|g4OTNpPkG4N\|c5PzF\|PD;hQi=>
MT4	MkfrRY51cX[rcnHsJIF{e2G7			M1\GbGFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXjFiM1KgbY5n\WO2ZXSgbY4hcHWvYX6gUXQ1KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[geolz[WxvaX7keYNm\CCleYTvdIF1cGmlIHXm[oVkfCCkeTDNWHQh[XO\|YYmsJGVEPTBiPTCwMlAxPzhizszNMi=>	NV:3XHNQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki5OVExQTVpPkK4PVUyODl3PD;hQi=>
MT-4	NFnt[VNCdnSrdnnyZYwh[XO\|YYm=			MV\BcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYyKDOEIHnu[oVkfGWmIHnuJIh2dWGwIF3UMVQh[2WubIOgZpkhfHexIH\vcIQh\GmudYTpc44hdWW2aH;kJIlvKHC{ZYPlcoNmKG:oIEGwKUBHSlNuIFXDOVAhRSByLkCwPEDPxE1w	NFnpd3o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUGwOFAyOCd-MUmxNFQxOTB:L3G+
MT-4	MXzBcpRqfmm{YXygZZN{[Xl?			Mnn6RY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXKDFiTly0MlMhcW62ZXfyZZNmKFN{M{DOJI12fGGwdDDpcoZm[3SnZDDpckBpfW2jbjDNWE01KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[geolzfXNvaX7keYNm\CCleYTvdIF1cGmlIHXm[oVkfCCkeTDNWHQh[XO\|YYmsJGVEPTBiPTCwMlAxQSEQvF2u	NWexZolFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUizO\|g4OTNpPkG4N\|c5PzF\|PD;hQi=>
MT4	MmDGRY51cX[rcnHsJIF{e2G7		NYTZc5BvPDhidH:gO\|IhcHK\|	MWrBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYyKGmwZnXjeIVlKGmwIHj1cYFvKE2WNDDj[YxteyCneIDy[ZN{cW6pIFfGVEBqdmO3YnH0[YQh\m:{IES4JJRwKDd{IHjyd{BqdiCjYoPlcoNmKG:oIEWwKUBvd3KvYXygbJVu[W5ic3XyeY0h[nlibYXseIlxdGVicn;1coQhfmm{YXygdoVxdGmlYYTpc44hc2mwZYTpZ5Mh[XO\|YYmsJGlRKD1iMD6wNFkh\|ryPLh?=	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjN7N{m2OUc,OjZ\|OUe5OlU9N2F-
FL-4	MXrBcpRqfmm{YXygZZN{[Xl?			NHLZcoVCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBH\WyrbnWgbY1ufW6xZHXmbYNq\W6leTD2bZJ2eyCrbn\lZ5Rm\CCrbjDjZZQhTkxvNDDj[YxteyCjc4Pld5Nm\CCjczD2bZJidCCUTlGgdJJw\HWldHnvckBjgSCUVD3xVGNTNCCHQ{WwJF0hOC5yMEm5PEDPxE1w	NHvzZ4U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEixN\|c{Oid-MkS4NVM4OzJ:L3G+
MT-4	MXHBcpRqfmm{YXygZZN{[Xl?			NFjjXJVCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZiMTDSTW4hcGG{Yn;ybY5oKGmwdHXndoF{\SCpZX7lJIlv\mWldHXkJIlvKE2WLUSgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iC4aYL1d{1qdmS3Y3XkJIN6fG:yYYTobYMh\W[oZXP0JIJ6KE2WVDDhd5NigSCjZoTldkAzOCCyYYPzZYdmeyC\|ZXzlZ5Rm\CCrbjDwdoV{\W6lZTDv[kBkd22yb4Xu[EwhTUN3MDC9JFAvODFizszNMi=>	MlTKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh\|N{i3NVMoRjF6M{e4O\|E{RC:jPh?=
HeLa	NGW2U25CdnSrdnnyZYwh[XO\|YYm=		MXK0PEBpenN?	NVXQWVRlSW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhXlOYLVegdJNmfWSxdInw[YQhUEmYMTDs[Y51cX[rcnHsJJBienSrY3zld{Bqdm[nY4Tl[EBqdiCqdX3hckBJ\UyjIHPlcIx{KGmwY4XiZZRm\CCob4KgOFghcHK\|IHL5JJNx\WO2cn;mcJVwem:vZYTyfUwhUUN3MDC9JFAvODFizszNMi=>	MofHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ6NUizNFAoRjJ{OEW4N\|AxRC:jPh?=
cat FL-4	MkHlRY51cX[rcnHsJIF{e2G7		MVu3JIRigXN?	NFz3ZohCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBH\WyrbnWgbY1ufW6xZHXmbYNq\W6leTD2bZJ2eyCrbn\lZ5Rm\CCrbjDjZZQhTkxvNDDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKH[rcnHsJJJmeGyrY3H0bY9vKGGodHXyJFch\GG7czDifUByfWGwdHn0ZZRqfmViUmStVGNTKGGwYXz5d4l{NCCHQ{WwJF0hOC5yMTFOwG0v	MmPTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5MEK4OFkoRjJ3N{CyPFQ6RC:jPh?=
cat FL-4	MmnYRY51cX[rcnHsJIF{e2G7		NFvxW2w4KGSjeYO=	NEjrZ21CdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBHUVZiaX7m[YN1\WRiaX6gZ4F1KE[OLUSgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKH[rcnHsJHJPSSCuZY\lcEBu\WG\|dYLl[EBi\nSncjC3JIRigXNiYomgdXJVNVCFUjDhcoFtgXOrczygSWM2OCB;IECuNFEh\|ryPLh?=	NIXwfYM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MUO5OVUyOCd-M{GzPVU2OTB:L3G+
MT4	NVi0SJVkSW62aY\pdoFtKGG\|c3H5			MYXBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYzKFKRRDCzRkBqdm[nY4Tl[EBqdiCqdX3hckBOXDRiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kB3cXKjbD3pcoR2[2WmIHP5eI9x[XSqaXOg[YZn\WO2IHL5JG1VXCCjc4PhfUwhTUN3MDC9JFAvODFzIN88UU4>	NV7PTmxFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki5OVExQTVpPkK4PVUyODl3PD;hQi=>
MT4	MVTBcpRqfmm{YXygZZN{[Xl?			MorRRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTJVu[W5iaX3teY5w\GWoaXPp[Y5kgSC4aYL1d{AyKDOEIHnu[oVkfGWmIHnuJG1VPCClZXzsd{Bie3Onc4Pl[EBieyCycn;0[YN1cW:wIHHnZYlve3RidnnyeZMucW6mdXPl[EBkgXSxcHH0bIlkKGWoZnXjeEBu\WG\|dYLl[EA2KGSjeYOgdI9{fCCrbn\lZ5Rqd25iYomgUXRVKGG\|c3H5MEBGSzVyIE2gNE4xOTF5IN88UU4>	M37mUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7OUSwOFYzLz5{OUm0NFQ3OjxxYU6=
MT4	Mo\SRY51cX[rcnHsJIF{e2G7			NGX2TnNCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZzIEPCJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[geolz[WxvaX7keYNm\CCleYTvdIF1cGmlIHXm[oVkfCCrbjDoeY1idiCPVESgZ4VtdHNuIFXDOVAhRSByLkCxN{DPxE1w	Ml;hQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh2MUezOFIoRjF6NEG3N\|QzRC:jPh?=
MT4	Mlz4RY51cX[rcnHsJIF{e2G7			MVLBcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYyKGmwZnXjeIVlKGmwIHj1cYFvKE2WNDDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKH[rcoXzMYlv\HWlZXSgZ5l1d3CjdHjpZ{Bm\m[nY4SsJGVEPTBiPTCwMlAyOyEQvF2u	NYn1U2ZKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC2N\|A4PjVpPkKwOlMxPzZ3PD;hQi=>
MT4	Mo\oRY51cX[rcnHsJIF{e2G7			NFTIbZhCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZzIEPCJIlv\mWldHXkJIlvKGi3bXHuJG1VPCClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJJZqenW\|LXnu[JVk\WRiY4n0c5BifGirYzDl[oZm[3RiYomgUXRVKGG\|c3H5MEBGSzVyIE2gNE4xOTNizszNMi=>	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTJ{N{W1NEc,OjF{Mke1OVA9N2F-
BL21(DE3)	MYDGeY5kfGmxbjDhd5NigQ>?		MmW4NUBpeg>?	MkL0TY5pcWKrdHnvckBw\iC{ZXPvcYJqdmGwdDDITXYuOSCrboTl[5Jie2Vic4ThcoQhfHKjboPm[ZIh[WO2aY\peJkh\XiycnXzd4VlKGmwIFXzZ4hmemmlaHnhJINwdGliQlyyNUhFTTNrIHPlcIx{KHW\|aX7nJFMzWC2uYXLlcIVlKESQQTDzeYJ{fHKjdHWgZYZ1\XJiMTDodkBjgSCmZX7zbZRwdWW2cnnjJIFv[Wy7c3nzMEBKSzVyIE2gNE4xOTNizszNMi=>	NXnSZ\|VURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[0OVE4PzFpPkK2OFUyPzdzPD;hQi=>
MT-4	MVHBcpRqfmm{YXygZZN{[Xl?			MY\BcpRqfmm{YXygZYN1cX[rdImgZYdicW6\|dDDITXYhOSCQTESuN{BqdnSnZ4Lhd4UhTTl{UTDteZRidnRiaX7m[YN1\WRiaX6gbJVu[W5iTWStOEBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oII\pdpV{NWmwZIXj[YQh[3m2b4DheIhq[yCnZn\lZ5Qh[nliTWTUJIF{e2G7LDDFR\|UxKD1iMD6wNVUh\|ryPLh?=	NXTpZ4x3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUizO\|g4OTNpPkG4N\|c5PzF\|PD;hQi=>
MT4	MkDxRY51cX[rcnHsJIF{e2G7		MoTiOUBl[Xm\|	M4DtfGFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXjFiM1KgbY5n\WO2ZXSgbY4hcHWvYX6gUXQ1KGOnbHzzJIlv[3WkYYTl[EBnd3JiNTDkZZl{KGK7IF3UWEBie3OjeTygSWM2OCB;IECuNFE2KM7:TT6=	NEj2NYM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MUOyOFU3Oid-M{GzNlQ2PjJ:L3G+
MT2	NEW0dWNCdnSrdnnyZYwh[XO\|YYm=			M2r0eGFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXiCrbjDNWFIh[2WubIOgbY4heHKnc3XuZ4Uhd2ZiM{WgcYcwdUxiaIXtZY4he2W{dX2gZYxjfW2rbjygSWM2OCB;IECuNFE3KM7:TT6=	NXrCO4RqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUiyNFc{QThpPkG4NlA4Ozl6PD;hQi=>
MT-4	MVnBcpRqfmm{YXygZZN{[Xl?		NFL0bJI2KGSjeYO=	M2jXXmFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXjFiM1KvUGFKKGmwZnXjeIVlKGmwIHj1cYFvKE2WLUSgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iC4aYL1d{1qdmS3Y3XkJIN6fG:yYYTobYMh\W[oZXP0JI1m[XO3cnXkJJN2en[rdnHsJIFnfGW{IEWg[IF6eyCkeTDNWHQh[XO\|YYmsJGVEPTBiPTCwMlAyPiEQvF2u	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF{NEmxPUc,OjRzMkS5NVk9N2F-
HeLa-CD4-LTR-beta-gal	MnnrRY51cX[rcnHsJIF{e2G7		MUixJIRigQ>?	NV\NWVN6SW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYLUGgN2IhcW6oZXP0[YQhcW5iaIXtZY4hUGWOYT3DSFQuVFSULXLleIEu\2GuIHPlcIx{KGGodHXyJFEh\GG7IHL5JJNx\WO2cn;zZ49xcWNiYX7hcJl{cXNuIFXDOVAhRSByLkCxOkDPxE1w	NWK0eJRiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2NlkzPTZpPkK1OlI6OjV4PD;hQi=>
MT-2	Mk[wRY51cX[rcnHsJIF{e2G7			MmDFRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOSB\|QjDpcoZm[3SnZDDpckBpfW2jbjDNWE0zKGOnbHzzJIJ6KHS5bzDmc4xlKGSrbIX0bY9vKG2ndHjv[EBqdiCycnXz[Y5k\SCxZjCxNEUhTkKVLDDIV2Eh[W6mIHHsdIhiOS2DR2CsJGVEPTBiPTCwMlAyQCEQvF2u	M4HRPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7MUC0NFExLz5zOUGwOFAyODxxYU6=
MT4	NVjyU2dHSW62aY\pdoFtKGG\|c3H5			NESxVnRCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZzIEPCJIlvKGi3bXHuJG1VPCClZXzsd{BqdiCycnXz[Y5k\SCxZjCxNEUhcGWjdD3hZ5RqfmG2ZXSg[oV1[WxiYn;2bY5mKHOncoXtMEBKSzl3IE2gNE4xOTlizszNMi=>	NHHJb2c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEe2N\|c2OSd-MUi3OlM4PTF:L3G+
MT2	MUnBcpRqfmm{YXygZZN{[Xl?		NUTITItbPSCmYYnz	NWHpeVRoSW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYMTCzRkBqdm[nY4Tl[EBqdiCqdX3hckBOXDJiY3XscJMh[W[2ZYKgOUBl[Xm\|IHL5JINp\W2rbIXtbY5me2OnbnPlJIlvKHC{ZYPlcoNmKG:oIHj1cYFvKHOncoXtJIFt[nWvaX6sJGVEPTBiPTCwMlAzKM7:TT6=	NGi2[WY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUK4OVM5QSd-MUmyPFU{QDl:L3G+
MT4	NFnRT5dCdnSrdnnyZYwh[XO\|YYm=		NVi2ZmsxPSCmYYnz	MmKxRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOiCUT1SgbY5n\WO2ZXSgbY4hcHWvYX6gUXQ1KGOnbHzzJIlv[3WkYYTl[EBnd3JiNTDkZZl{KGK7IF3UWEBie3OjeTygSWM2OCB;IECuNFIh\|ryPLh?=	NXjnUJpyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{GzNlQ2PjJpPkOxN\|I1PTZ{PD;hQi=>
TZM-b1	M2HBfGFvfGm4aYLhcEBie3OjeR?=		MVGxJIhz	MlPBRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXNTFiTly0MlMhcW6oZXP0[YQhcW5iaIXtZY4hXFqPLXKxJINmdGy\|IIDy[ZRz\WG2ZXSg[o9zKDFiaIKg[o9tdG:5ZXSgZpkhfmm{YXygbY5n\WO2aX;uJI1m[XO3cnXkJIFnfGW{IEKg[IF6eyCkeTDDVHJIKGG\|c3H5MEBKSzVyIE2gNE4xOjFizszNMi=>	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDRyOEKyOEc,Ojh2MEiyNlQ9N2F-
CEM-SS	M3XLVWFvfGm4aYLhcEBie3OjeR?=		NHr5TIE3KGSjeYO=	Mn\1RY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOSB\|QjDpcoZm[3SnZDDpckBpfW2jbjDDSW0uW1NiY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIH;mJJZqenW\|LXnu[JVk\WRiY4n0c5BifGirYzDl[oZm[3RiYX\0[ZIhPiCmYYnzJIJ6KE2WUzDhd5NigSxiRVO1NEA:KDBwMEKzJO69VS5?	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzJ6M{K2NUc,Ojd{OEOyOlE9N2F-
HeLa	NFHqWnJCdnSrdnnyZYwh[XO\|YYm=		Mmn2N{Bl[Xm\|	MlPKRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOSB\|QjDpcoZm[3SnZDDpckBpfW2jbjDI[WxiKGOnbHzzJIV5eHKnc4PpcochS0R2LVzUVk1j\XSjLXfhcEBie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJJZqemGuIILldIxq[2G2aX;uJIFnfGW{IEOg[IF6eyCkeTDy[ZBwenSncjDn[Y5mKGG\|c3H5MEBGSzVyIE2gNE4xOjN4IN88UU4>	NWTGfJZIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS2PFQzPzBpPkK0Olg1OjdyPD;hQi=>
HeLa-CD4-LTR-beta-gal	NFzKTJhCdnSrdnnyZYwh[XO\|YYm=			M4m5e2FvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXi1zIEPCJIlv\mWldHXkJIlvKGi3bXHuJGhmVGFvQ1S0MWxVWi2kZYThMYdidCClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJJZqemGuIILldIxq[2G2aX;uJIJ6KFOyZXP0doFO[XhiR1XNTW5KNViVIIDsZZRmKHKnYXTldkBidmGueYPpd{whTUN3MDC9JFAvODJ\|NjFOwG0v	NFX5VXg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUm2NVk3OCd-MkW5OlE6PjB:L3G+
HeLa	M164bWFvfGm4aYLhcEBie3OjeR?=		MX6yJIRigXN?	NVXiSmZnSW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYMTCzRkBqdm[nY4Tl[EBqdiCqdX3hckBJ\UyjIHPlcIx{KGW6cILld5NqdmdiQ1S0JIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[geolz[WxicnXwcIlk[XSrb36gZYZ1\XJiMjDkZZl{KGK7IHLleIEu\2GuYXP0c5Nq\GG\|ZTDy[ZBwenSncjDn[Y5mKGG\|c3H5MEBGSzVyIE2gNE4xOjRizszNMi=>	NGPkVpI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEGyOFkyQSd-MkSxNlQ6OTl:L3G+
MT-4	M2mzeWFvfGm4aYLhcEBie3OjeR?=			NU\wPWo1SW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYIEGgVmlPKEiLVjCxJHJKViCqYYLic5JqdmdiaX70[Ydz[XOnIHflcoUhcW6oZXP0[YQhcW5iTWStOEBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oII\pdpV{NWmwZIXj[YQh[3m2b4DheIhq[yCnZn\lZ5Qh[nliTWTUJIF{e2G7IHHmeIVzKDRyIIDhd5Ni\2W\|IIPlcIVkfGWmIHnuJJBz\XOnbnPlJI9nKGOxbYDveY5lNCCHQ{WwJF0hOC5yMkWg{txONg>?	NFTtcXQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOEO3PFcyOyd-MUizO\|g4OTN:L3G+
TZM-bl	NXfrRoVCSW62aY\pdoFtKGG\|c3H5		MV20PEBpenN?	NInXfnVCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJfW2jbjDpcY12dm:mZX\pZ4lmdmO7II\pdpV{KDFiaX7m[YN1\WRiaX6gbJVu[W5iVGrNMYJtKGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[geolz[WxicnXwcIlk[XSrb36gZYZ1\XJiNEigbJJ{KGK7IHnueoVzfGWmIH3pZ5Jwe2OxcHnjJIFv[Wy7c3nzMEBGSzVyIE2gNE4xOjVizszNMi=>	NWS5b5A1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKxOVQ4PjJpPkKyNVU1PzZ{PD;hQi=>
MT4	MoTHSpVv[3Srb36gZZN{[Xl?		M{nRbVEhcHJ?	NYThbVVnUW6qaXLpeIlwdiCxZjD3bYxlKHS7cHWgTGlXOSB\|QjDpcoZm[3SnZDDpckBpfW2jbjDNWFQh[2WubIOgeZNqdmdiY3XscJMheHKnLXnuZ5Vj[XSnZDD3bZRpKGOxbYDveY5lKG[xcjCxJIhzKG2nYYP1doVlKDRiZHH5d{Bxd3O2II\pdoFtKGmwZnXjeIlwdiCrbjDwdoV{\W6lZTDv[kAzOCCvZz;tcEBJW0FiYomgUXRVKGG\|c3H5MEBKSzVyIE2gNE4xOjlizszNMi=>	M3LtSlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OU[zNVM2Lz5{Mkm2N\|E{PTxxYU6=
P4R5 MAGI	MmrZRY51cX[rcnHsJIF{e2G7		NYTGRWE2OjRiaILz	MkTQRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOSCrbn\lZ5Rm\CCrbjDDSFQwS1iFUkSvR2NTPSCneIDy[ZN{cW6pIHj1cYFvKFB2UkWgUWFIUSClZXzsd{BxemWrbnP1ZoF1\WRid3n0bEBk\WyuczDmc5IhOjRiaILzJIZwdGyxd3XkJIJ6KH[rcnHsJIlv\mWldHnvckBu\WG\|dYLl[EBi\nSncjC0PEBpenNiYomgZoV1[S2pYXzhZ5Rwe2mmYYPlJJJmeG:{dHXyJIdmdmViYYPzZZktKEWFNUCgQUAxNjB\|IN88UU4>	NIrNc2U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MECzNVk4Pid-M{CwN\|E6PzZ:L3G+
P4R5	Mni2RY51cX[rcnHsJIF{e2G7		NF3pe2czPCCqcoO=	MnH0RY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOSCrbn\lZ5Rm\CCrbjDDSFQwS1iFUkSvR2NTPSCneIDy[ZN{cW6pIHj1cYFvKFB2UkWgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iC4aYLhcEBz\XCuaXPheIlwdiCycnXpcoN2[mG2ZXSge4l1cCClZXzsd{Bnd3JiMkSgbJJ{KG[xbHzve4VlKGK7II\pdoFtKGmwZnXjeIlwdiCvZXHzeZJm\CCjZoTldkA1QCCqcoOgZpkh[mW2YT3nZYxi[3Sxc3nkZZNmKHKncH;yeIVzKGenbnWgZZN{NCCHQ{WwJF0hOC5yMzFOwG0v	MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDV{NUK3PUc,Ojh3MkWyO\|k9N2F-
P4R5	NGW5OGtCdnSrdnnyZYwh[XO\|YYm=		NXr1fpJFOjRiaILz	NVT3PXNkSW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYMTDpcoZm[3SnZDDpckBpfW2jbjDQOHI2KGOnbHzzJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCrbjD2bZJidCCrbn\lZ5Rqd25icILlbY5kfWKjdHXkJJdqfGhiY3XscJMh\m:{IEK0JIhzeyCob3zsc5dm\CCkeTD2bZJidCCrbn\lZ5Rqd25ibXXhd5Vz\WRiYX\0[ZIhPDhiaILzJIJ6KG[udX;y[ZNk\W6lZTDiZZNm\CCkZYThMYdidGGldH;zbYRie2VicnXwc5J1\XJiZ3Xu[UBj[XOnZDDNRWdKKGG\|LDDFR\|UxKD1iMD6wN{DPxE1w	NV7qcXF[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmwN\|ExPjJpPkK5NFMyODZ{PD;hQi=>
P4R5	MnTwRY51cX[rcnHsJIF{e2G7		NGnLSG4zPCCqcoO=	M3foTGFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXi1zIHnu[oVkfGWmIHnuJIh2dWGwIGC0VlUh[2WubIOgZZN{\XO\|ZXSgZZMhemWmdXP0bY9vKGmwII\pdoFtKHKncHzpZ4F1cW:wIIDy[Ylv[3WkYYTl[EBnd3JiMkSgbJJ{KG[xbHzve4VlKGK7II\pdoFtKGmwZnXjeIlwdiCjbnSgcYVie3W{ZXSgZYZ1\XJiNEigbJJ{KGK7IF3BS2kh[XO\|YYmsJGVEPTBiPTCwMlA{KM7:TT6=	MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODd\|OUiyNkc,OzB5M{m4NlI9N2F-
P4R5	MVHBcpRqfmm{YXygZZN{[Xl?		MXuyOEBpenN?	NHjh[pVCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZzIHnu[oVkfGWmIHnuJIh2dWGwIGC0VlUh[2WubIOgZZN{\XO\|ZXSgZZMhemWmdXP0bY9vKG:oII\pdpV{KHKncHzpZ4F1cW:wIIDy[Ylv[3WkYYTl[EB4cXSqIHPlcIx{KG[xcjCyOEBpenNiZn;scI94\WRiYomgeolz[WxiaX7m[YN1cW:wIH\vdkA1QCCqcoOgZpkhPC2vZYTofYx2dWKnbHzp[oVzgWypYXzhZ5Rwe2mmZT3iZZNm\CCPQVfJJIF{e2G7LDDFR\|UxKD1iMD6wN{DPxE1w	M3\rV\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5MkizNlYyLz5{N{K4N\|I3OTxxYU6=
MT4	NXLsT4UySW62aY\pdoFtKGG\|c3H5			M3rWcWFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXjFiM1KgbY4hcHWvYX6gUXQ1KGOnbHzzJIlvKHC{ZYPlcoNmKG:oIEWwKUBvd3KvYXygbJVu[W5ic3XyeY0tKEmFOUWgQUAxNjB\|MTFOwG0v	NVn3XXFkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi3OlM4PTFpPkG4O\|Y{PzVzPD;hQi=>
MT4	NYTqPXVKSW62aY\pdoFtKGG\|c3H5		NGjHUJo1QCC2bzC3NkBpenN?	NGDXVoFCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZzIHnu[oVkfGWmIHnuJIh2dWGwIF3UOEBk\WyuczDlfJBz\XO\|aX7nJGdHWCCrbnP1ZoF1\WRiZn;yJFQ5KHSxIEeyJIhzeyCrbjDwdoV{\W6lZTDv[kA2OCVibn;ycYFtKGi3bXHuJJNmenWvIHL5JI12dHSrcHzlJJJwfW6mII\pdoFtKHKncHzpZ4F1cW:wIHvpcoV1cWO\|IHHzd4F6NCCLUDC9JFAvODV\|IN88UU4>	M3W4R\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4M{m3PVY2Lz5{NkO5O\|k3PTxxYU6=
BL21(DE3)	M2rxbmZ2dmO2aX;uJIF{e2G7		NGntcmcyKGi{	MVjJcohq[mm2aX;uJI9nKEyHRFfGM5A4PS2mZYDlcoRmdnRiZoXscEBt\W6pdHigTGlXNTFiaX70[Ydz[XOnIHX4dJJme3OnZDDpckBGe2OqZYLpZ4hq[SClb3zpJGJNOjFqRFWzLUBk\WyuczDwdoVqdmO3YnH0[YQh\m:{IEGgbJIh\nW{dHjldkBqdmO3YnH0[YQh\m:{IEmwJI1qdnNid3n0bEBjcW:2aX6tcIFj\WynZDDkc45weiCGTlGgZY5lKHSjcnfleEBFVkFiYomgTHRTTiCjc4PhfUwhUUN3MDC9JFAvODV6IN88UU4>	M1\5UVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNzNESyOlg1Lz5\|MUS0NlY5PDxxYU6=
MT-4	NWnTW3RVSW62aY\pdoFtKGG\|c3H5			MmjBRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXKDFiUlnOJGhKXiBzIGLJUkBp[XKkb4LpcochcW62ZXfyZZNmKGenbnWgbY5n\WO2ZXSgbY4hVVRvNDDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKH[rcoXzMYlv\HWlZXSgZ5l1d3CjdHjpZ{Bm\m[nY4SgZpkhVVSWIHHzd4F6KGGodHXyJFYxKHCjc4Ph[4V{KHOnbHXjeIVlKGmwIIDy[ZNmdmOnIH;mJINwdXCxdX7kMEBGSzVyIE2gNE4xPjhizszNMi=>	MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDN5OEexN{c,OTh\|N{i3NVM9N2F-
HeLaT4	MoWzRY51cX[rcnHsJIF{e2G7			NXvEVpA5SW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5Qhe2mwZ3zlMZJwfW6mIFjJWlEhVky[Llz1fE1TKGijcnLvdolv\yCrbnHjeIl3[XSrbnegcZV1[XSrb37zJIlvKGWwdjygepBzKGGwZDDjZZJzcWW\|IH\pdoVndHlibIXjbYZmemG\|ZTDn[Y5mKGmwIIDsZYNmKG:oIH7l[kBie3Onc4Pl[EBieyCuZY\lcEBw\iB{IH3pcpMhdWGpbnX0bYMhdmGwb4DhdpRq[Wy\|LX3l[IF1\WRiaX7m[YN1cW:wIHnuJIh2dWGwIFjlUIFVPCClZXzsd{B1emWjdHXkJIZweiBzLDDFR\|kyKD1iMD6wO\|Mh\|ryPLh?=	MmexQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFyNkCxNFgoRjJzME[wNVA5RC:jPh?=
HeLa-T4	M2PQbmFvfGm4aYLhcEBie3OjeR?=		M2XaOFQ5KGi{cx?=	M4q0ZmFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JJNqdmeuZT3yc5Vv\CCKSW[xJG5NYC6OdYitVkBp[XKkb4LpcochcW6jY4TpeoF1cW6pIH31eIF1cW:wczDpckBmdnZuII\wdkBidmRiY3HydolmeyCoaYLl[ox6KGy3Y3nm[ZJie2ViZ3Xu[UBqdiCybHHj[UBw\iCwZX[gbY5n\WO2ZXSgbY4hcHWvYX6gTIVN[S2WNDDj[YxteyCjc4Pld5Nm\CCjczDseYNq\mW{YYPlJIFkfGm4aYT5JIFnfGW{IES4JIhzeyCkeTDlfI9o\W6xdYOgVnQh[XO\|YYmsJGVEPTBiPTCwMlA4PyEQvF2u	M1vOW\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzME[wNVA5Lz5{MUC2NFExQDxxYU6=
TZM-bl	M{T0cmFvfGm4aYLhcEBie3OjeR?=		Mn7rOFghcHK\|	M1jRPGFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXi1zIHnu[oVkfGWmIHnuJIh2dWGwIGTaUU1jdCClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJJZqemGuIILldIxq[2G2aX;uJIZweiB2ODDodpMh[nliYoLp[4h1NUeubzDseYNq\mW{YYPlJIF{e2G7LDDFR\|UxKD1iMD6xOUDPxE1w	NUPFbo9ZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[0PFc6OTNpPkK2OFg4QTF\|PD;hQi=>
HOS	MkWzRY51cX[rcnHsJIF{e2G7		NHXXT2I{KGi{cx?=	M{XOTWFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGh2dWGwIHntcZVvd2SnZnnjbYVv[3lidnnyeZMhOSCqYYLic5JqdmdiaX70[Ydz[XOnIF6xOVVJKG23dHHueEBqdm[nY4Tl[EBqdiCKT2OgZ4VtdHNicILlbY5kfWKjdHXkJIZweiB\|IHjyd{Bnd2yub4fl[EBjgSC4aYLhcEBqdm[nY4Tpc44hdWWjc4Xy[YQh[W[2ZYKgOFghcHK\|IHL5JIx2[2moZYLhd4UhemWyb4L0[ZIh\2WwZTDhd5NigSxiRVO1NEA:KDBwMUW0JO69VS5?	MnzSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2N{G4NVYoRjJ2NEexPFE3RC:jPh?=
TZM-bl	Mnz5RY51cX[rcnHsJIF{e2G7			M{DXS2FvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXjFiTly0MlMhcW6oZXP0[YQhcW5iaIXtZY4hXFqPLXLsJINmdGy\|IH3lZZN2emWmIIXweI8hOjRiaILzJIJ6KGK{aXfoeEBIdG9vbIXjbYZmemG\|ZTDy[ZBwenSncjDn[Y5mKGG\|c3H5MEBKSzVyIE2gNE4yPiEQvF2u	M4TSNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNzNUW3OlA6Lz5\|MUW1O\|YxQTxxYU6=
HOS	MnjrRY51cX[rcnHsJIF{e2G7		MmHNN{BpenN?	NHXDO5pCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJfW2jbjDpcY12dm:mZX\pZ4lmdmO7II\pdpV{KDFiaHHyZo9zcW6pIHnueIVoemG\|ZTDZNVQ{WiCvdYThcpQhcW6oZXP0[YQhcW5iSF;TJINmdGy\|IIDy[Ylv[3WkYYTl[EBnd3JiMzDodpMh\m:ubH;3[YQh[nlidnnyZYwhcW6oZXP0bY9vKG2nYYP1doVlKGGodHXyJFQ5KGi{czDifUBtfWOrZnXyZZNmKHKncH;yeIVzKGenbnWgZZN{[XluIFXDOVAhRSByLkG2NkDPxE1w	NFvSXms9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES3NVgyPid-MkS0O\|E5OTZ:L3G+
TZM-bl	NGfmW3NCdnSrdnnyZYwh[XO\|YYm=		NFLMVpcyKGi{	NXHDdY1mSW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYMTDOUFQvOyCrbn\lZ5Rm\CCrbjDoeY1idiCWWl2tZowh[2WubIOg[ZhxemW\|c3nu[{BEYEOUND30do9xcWNiaX7jeYJifGWmIH\vdkAyKGi{IIDybY9zKHSxIHnu[oVkfGmxbjDt[YF{fXKnZDDh[pRmeiB2ODDodpMh[nlibIXjbYZmemG\|ZTDy[ZBwenSncjDn[Y5mKGG\|c3H5MEBKSzVyIE2gNE42KM7:TT6=	MnPwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR{OUGwOFIoRjJ2MkmxNFQzRC:jPh?=
TZM-bl	NV:5Xo5GSW62aY\pdoFtKGG\|c3H5		MVexJIhz	MnvIRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOSCQTESuN{Bqdm[nY4Tl[EBqdiCqdX3hckBVYk1vYnygZ4VtdHNiZYjwdoV{e2mwZzDDXGNTPC22cn;wbYMhcW6ldXLheIVlKG[xcjCxJIhzKHC{aX;yJJRwKGmwZnXjeIlwdiCvZXHzeZJm\CCjZoTldkA1QCCqcoOgZpkhdHWlaX\ldoF{\SC{ZYDvdpRmeiCpZX7lJIF{e2G7LDDJR\|UxKD1iMD61NFEyQSEQvF2u	MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDJ7MUC0Nkc,OjR{OUGwOFI9N2F-
HeLa-T4	NVrZeoVqSW62aY\pdoFtKGG\|c3H5		MUW0PEBpenN?	NIXuNINCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEB{cW6pbHWtdo92dmRiSFnWNUBPVFhwTIX4MXIhcGG{Yn;ybY5oKGmwYXP0bZZifGmwZzDteZRifGmxboOgbY4h\W64LDD2dJIh[W6mIHPhdpJq\XNiZnny[YZtgSCudXPp[oVz[XOnIHflcoUhcW5icHzhZ4Uhd2ZibnXmJIlv\mWldHXkJIlvKGi3bXHuJGhmVGFvVESgZ4VtdHNiYYPz[ZN{\WRiYYOgcJVkcW[ncnHz[UBi[3Srdnn0fUBi\nSncjC0PEBpenNiYomg[Zhw\2Wwb4XzJHJVKGG\|c3H5MEBGSzl3IE2gNE45OSEQvF2u	MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTB4MEGwPEc,OjFyNkCxNFg9N2F-
HOS	Mo[xRY51cX[rcnHsJIF{e2G7		NIrXdos{KGi{cx?=	M3HURWFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGh2dWGwIHntcZVvd2SnZnnjbYVv[3lidnnyeZMhOSCqYYLic5JqdmdiaX70[Ydz[XOnIFexOFBUN1FzNEjIJIRwfWKuZTDteZRidnRiaX7m[YN1\WRiaX6gTG9UKGOnbHzzJJBz\WmwY4XiZZRm\CCob4KgN{BpenNiZn;scI94\WRiYomgeolz[WxiaX7m[YN1cW:wIH3lZZN2emWmIHHmeIVzKDR6IHjyd{BjgSCudXPp[oVz[XOnIILldI9zfGW{IHflcoUh[XO\|YYmsJGVEPTBiPTCxMlkh\|ryPLh?=	MnSyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2N{G4NVYoRjJ2NEexPFE3RC:jPh?=
MT2	MlHKRY51cX[rcnHsJIF{e2G7		MX2zJJRwKDRiZHH5dy=>	M4PCT2FvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXjFiTly0MVMhcGG{Yn;ybY5oKEdzNEDTM3EyPDiKIH31eIFvfCCrbn\lZ5Rm\CCrbjDoeY1idiCPVEKgZ4VtdHNibXXhd5Vz\WRiYX\0[ZIhOyC2bzC0JIRigXNiYomgcJVkcW[ncnHz[UBz\XCxcoTldkBo\W6nIHHzd4F6NCCHQ{WwJF0hOi52MjFOwG0v	NXOwUHJ[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{KwPFExOTBpPkOyNFgyODFyPD;hQi=>
HeLaT4	MnPqRY51cX[rcnHsJIF{e2G7		NYjlcmN2OjRiaILz	Mke0RY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4Sgd4lv\2ynLYLveY5lKEiLVkGgUmxZNky3eD3SJIhiemKxcnnu[{BqdmGldHn2ZZRqdmdibYX0ZZRqd26\|IHnuJIVvfixidoDyJIFv\CClYYLybYV{KG[rcnXmcJkhdHWlaX\ldoF{\SCpZX7lJIlvKHCuYXPlJI9nKG6nZjDhd5Nme3OnZDDhd{Bt\X[nbDDv[kBqdm[nY4Tpc44hfXOrbnegbJVu[W5iSHXMZXQ1KGOnbHzzJJBz\XS{ZXH0[YQh\m:{IEK0JIhzeyCob3zsc5dm\CCkeTDlfJBwe2WmIITvJJZqNCCHQ{WwJF0hPC54IN88UU4>	NVHKXFJmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGwOlAyODhpPkKxNFYxOTB6PD;hQi=>
MT4	M1HWWWN6fG:2b4jpZ4l1gSCjc4PhfS=>		MYS1JIRigXN?	NYjQcFNpS3m2b4TvfIlkcXS7IHnuJI1w[2tvaX7m[YN1\WRiaIXtZY4hVVR2IHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDpckBk\WyuII\pZYJqdGm2eTDpcoN2[mG2ZXSg[o9zKDViZHH5d{BjgSCPVGSgZZN{[XluIFPDOVAhRSB4LkWxJO69VS5?	Mm\SQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzF\|MkS1OlIoRjNzM{K0OVYzRC:jPh?=
CHO	MW\GeY5kfGmxbjDhd5NigQ>?			MUDJcohq[mm2aX;uJI9nKHOub4eg[IVt[XmnZDDpcpdiemRicnXjeIlngWmwZzDwc5Rie3OrdX2gZ5VzemWwdDCoTYt{MSCrbjDDbIlv\XOnIFjhcZN1\XJiT4\hdpkhMEOKTzmgZ4VtdHNiZYjwdoV{e2mwZzDoT5ZNWVRzL3jtbY5MKG2nYYP1doVlKHW\|aX7nJGlwdlexcnvzJHF2[XS2cn:gZZV1d22jdHXkJJBifGOqIHPsZY1xKHCuYYTmc5JuNCCLQ{WwJF0hOjVwMUG4PUDPxE1w	Mn;tQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVyOEe3OVMoRjJ3MEi3O\|U{RC:jPh?=
U373-MAGI	M4H5UGFvfGm4aYLhcEBie3OjeR?=	MWO1NEBweiBzMECgcm0>	NHXub5Q4OiCqcoO=	M3XobGFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JHZUXi2JIIDz[ZVld3S7cHXkJGhKXi1zIF7MOE0{KGmwZnXjeIVlKGmwIHj1cYFvKFV\|N{OtUWFIUSClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25iaX6g[4FoKGyndnXsJIF1KDVyIH;yJFExOCCwTTDt[YF{fXKnZDDheEA4OiCqcoOgdI9{fCCrbn\lZ5Rqd25iYomgdXBEWiCvZYToc4Q>	M{PKdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5MUG3NlYxLz5{N{GxO\|I3ODxxYU6=
U373-MAGI	MWPBcpRqfmm{YXygZZN{[Xl?	NX25TYJ4PTBib4KgNVAxKG6P	NGfNN5A4OiCqcoO=	Ml3ERY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgWnNXNUdicIPleYRwfHmyZXSgTGlXNTFiTly0MVMhcW6oZXP0[YQhcW5iaIXtZY4hXTN5Mz3NRWdKKGOnbHzzJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCrbjDVOU1o[WdibHX2[Ywh[XRiNUCgc5IhOTByIH7NJI1m[XO3cnXkJIF1KDd{IHjyd{Bxd3O2IHnu[oVkfGmxbjDifUByWEOUIH3leIhw\A>?	NVjRSJFmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkexNVczPjBpPkK3NVE4OjZyPD;hQi=>
MT2	MX\BcpRqfmm{YXygZZN{[Xl?	NWjMNll7OSC3TR?=	NVzNUHpwOzBiaILz	M3vS[GFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JJdqdGRvdInw[UBJUVZzIF7MOE0{KGmwZnXjeIVlKGmwZnXjeIVlKGmwIHj1cYFvKE2WMjDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gbY4hUEmYMTDpcpRm\3KjdHXkJGRPSSCjdDCxJJVOKGGwZDDt[YF{fXKnZDDh[pRmeiB\|MDDodpMheG:\|dDDpcoZm[3Srb36gZpkhSWy3LVzUVkBRS1JicILveI9kd2xiYnHz[YQhdWW2aH;k	NF3TOXU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEm5Olc5OCd-M{C5PVY4QDB:L3G+

Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID

Western blot

CHOP / ATF-4 / XBP-1 / Lamin B

24625618

In vivo

Raltegravir induces viro-immunological improvement of nonhuman primates with progressing SIVmac251 infection. One non-human primate shows an undetectable viral load following Raltegravir monotherapy. ^[5]

Protocol (from reference)

Kinase Assay: ^[1]	PFV integration assay: For quantitative strand transfer assays, donor DNA substrate is formed by annealing HPLC grade oligonucleotides 5′-GACTCACTATAGGGCACGCGTCAAAATTCCATGACA and 5′-ATTGTCATG GAATTTTGACGCGTGCCCTATAGTGAGTC. Reactions (40 μL) contains 0.75 μM PFV IN, 0.75 μM donor DNA, 4 nM (300 ng) supercoiled pGEM9-Zf(−) target DNA, 125 mM NaCl, 5 mM MgSO₄, 4 μM ZnCl₂, 10 mM DTT, 0.8% (vol/vol) DMSO, and 25 mM BisTris propane–HCl, pH 7.45. Raltegravir is added at indicated concentrations. Reactions are initiated by addition of 2 μL PFV IN diluted in 150 mM NaCl, 2 mM DTT, and 10 mM Tris-HCl, pH 7.4, and stopped after 1 hour at 37 °C by addition of 25 mM EDTA and 0.5% (wt/vol) SDS. Reaction products, deproteinized by digestion with 20 μg proteinase K for 30 minutes at 37 °C followed by ethanol precipitation, are separated in 1.5% agarose gels and visualized by staining with ethidium bromide. Integration products are quantified by quantitative real-time PCR, using Platinum SYBR Green qPCR SuperMix and three primers: 5′-CTACTTACTCTAGCTTCCCGGCAAC, 5′-TTCGCCAGTTAATAGTTTGCGCAAC, and 5′-GACTCACTATAGGGCACGCGT. PCR reactions (20 μL) contained 0.5 μM of each primer and 1 μL diluted integration reaction product. Following a 5-min denaturation step at 95 °C, 35 cycles are carried out in a CFX96 PCR instrument, using 10 seconds denaturation at 95 °C, 30 seconds annealing at 56 °C and 1 minutes extension at 68 °C. Standard curves are generated using serial dilutions of WT PFV IN reaction in the absence of INSTI.
Cell Research: ^[5]	Cell lines: Human MT-4 cells Concentrations: 0.0001-1 μM Incubation Time: 5 days Method: Human MT-4 cells are infected for 2 hours with the SIVmac251, HIV-1 (IIIB) and HIV-2 (CDC 77618) stocks at a multiplicity of infection of, approximately, 0.1. Cells are then washed three times in phosphate buffered saline, and suspended at 5 × 10⁵/mL in fresh culture medium (to primary cells 50 units/mL of IL-2 are added) in 96-well plates, in the presence or absence of a range of triplicate raltegravir concentrations (0.0001 μM -1 μM). Untreated infected and mock-infected controls are prepared too, in order to allow comparison of the data derived from the different treatments. Viral cytopathogeniciy in MT-4 cells is quantitated by the methyl tetrazolium (MTT) method (MT-4/MTT assay) when extensive cell death in control virus-infected cell cultures is detectable microscopically as lack of capacity to re-cluster. The capability of MT-4 cells to form clusters after infection. Briefly, clusters are disrupted by pipetting; and, after 2 hours of incubation at 37 °C, the formation of new clusters is assessed by light microscopy (100 × magnification). Cell culture supernatants are collected for HIV-1 p24 and HIV-2/SIVmac251 p27 core antigen measurement by ELISA. In CEMx174-infected cell cultures, which show a propensity to form syncytia induced by the virus envelope glycoproteins, syncytia are counted, in blinded fashion, by light microscopy for each well at 5 days following infection.
Animal Research: ^[5]	Animal Models: Indian Rhesus macaques Dosages: 50 mg/kg or 100 mg/kg Administration: Oral administration

References

+ Expand

Solubility (25°C)

In vitro


In vivo	Add solvents to the product individually and in order (Data is from Selleck tests instead of citations): 2% DMSO+40% PEG 300+2% Tween 80+ddH2O For best results, use promptly after mixing. Click to purchase: PEG300 Tween 80	8mg/mL

Chemical Information

Molecular Weight	444.42
Formula	C₂₀H₂₁FN₆O₅
CAS No.	518048-05-0
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	CC1=NN=C(O1)C(=O)NC(C)(C)C2=NC(=C(C(=O)N2C)O)C(=O)NCC3=CC=C(C=C3)F

Download Raltegravir (MK-0518) SDF

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04513626	Recruiting	Drug: DORAVIRINE 100 MG [Pifeltro]	HIV Infections	Centre de Recherches et d''Etude sur la Pathologie Tropicale et le Sida	September 15 2020	Phase 2
NCT03667547	Completed	Drug: Raltegravir	Human Immunodeficiency Virus (HIV) Infection	Merck Sharp & Dohme LLC	September 27 2018	Phase 4
NCT03174977	Recruiting	Drug: 18F-Raltegravir	HIV-1-infection	University of California San Francisco\|Merck Sharp & Dohme LLC	April 1 2018	Early Phase 1

(data from https://clinicaltrials.gov, updated on 2022-08-01)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):