Xevinapant (AT406)

Catalog No.S2754 Synonyms: ARRY-334543, Debio1143, SM-406

For research use only.

Xevinapant (AT406, ARRY-334543, Debio1143, SM-406) is a potent Smac mimetic and an antagonist of IAP (inhibitor of apoptosis protein via E3 ubiquitin ligase), binding to XIAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with Ki of 66.4 nM, 1.9 nM, and 5.1 nM, 50- to 100-fold higher affinities than the Smac AVPI peptide. Phase 1.

Xevinapant (AT406) Chemical Structure

CAS No. 1071992-99-8

Selleck's Xevinapant (AT406) has been cited by 31 publications

Purity & Quality Control

Choose Selective IAP Inhibitors

Biological Activity

Description Xevinapant (AT406, ARRY-334543, Debio1143, SM-406) is a potent Smac mimetic and an antagonist of IAP (inhibitor of apoptosis protein via E3 ubiquitin ligase), binding to XIAP-BIR3, cIAP1-BIR3 and cIAP2-BIR3 with Ki of 66.4 nM, 1.9 nM, and 5.1 nM, 50- to 100-fold higher affinities than the Smac AVPI peptide. Phase 1.
Targets
cIAP1-BIR3 [1]
(cell-free assay)
cIAP2-BIR3 [1]
(cell-free assay)
XIAP-BIR3 [1]
(cell-free assay)
1.9 nM(Ki) 5.1 nM(Ki) 66.4 nM(Ki)
In vitro

AT-406 is a Smac mimetic and appears to mimic closely the AVPI peptide in both hydrogen bonding and hydrophobic interactions with XIAP, with additional hydrophobic contacts with W323 of XIAP. AT-406 is more sensitive to these IAPs than Smac AVPI peptide with 50-100 fold binding affinities. AT-406 (at 1 μM) completely restores the activity of caspase-9, which is suppressed by 500 nM XIAP BIR3 in a cell-free system. In MDA-MB-231 cell, AT-406 induces rapid cellular cIAP1 degradation and also pulls down the cellular XIAP protein. AT-406 effectively inhibits lots of human cancer cell lines and shows IC50 of 144 and 142 nM in MDA-MB-231 cell and SK-OV-3 ovarian cell, with low toxicity against normal-like human breast epithelial MCF-12F cells and primary human normal prostate epithelial cells. AT-406 induces apoptosis in MDA-MB-231 cell by inducing activation of caspase-3 and cleavage of PARP. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
EVSA-T NWe2SWo1S3m2b4TvfIlkcXS7IHHzd4F6 NYTXcJJuPzJiaILz MUDDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDz[Y5{cXSrdnWgSXZUSS2WIHPlcIx{KGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4Yh[2WubDDndo94fGhiYX\0[ZIhPzJiaILzJIJ6KEGuYX3hdkBDdHWnIHHzd4F6NCCHQ{WwJF0hOC5yMEKxJO69VS5? MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjJzOEK2OEc,OjZ{MUiyOlQ9N2F-
MDA-MB-231 M3zt[mN6fG:2b4jpZ4l1gSCjc4PhfS=> MWC3NkBpenN? M{DJbGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJJNmdnOrdHn2[UBOTEFvTVKtNlMyKGOnbHzzJIF{e2W|c3XkJIF{KGmwaHnibZRqd25ib3[gZ4VtdCCpcn;3eIgh[W[2ZYKgO|IhcHK|IHL5JGFt[W2jcjDCcJVmKGG|c3H5MEBGSzVyIE2gNE4xOTlizszNMi=> MnL2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{MUiyOlQoRjJ4MkG4NlY1RC:jPh?=
HEK293 MX3GeY5kfGmxbjDhd5NigQ>? MXSyJIhzew>? NV[1Z2pkSW62YXfvcol{fCCjY4Tpeol1gSCjdDDmeYxtNWynbnf0bEBHVEGJLYTh[4dm\CC[SVHQJEh2dmuwb4fuJI9zcWerbjmgeJJidnOoZXP0[YQhcW5iSFXLNlk{KGOnbHzzJIF{e2W|c3XkJIF{KGmwaHnibZRqd25ib3[gbY51\XKjY4Tpc44hf2m2aDDjZZNx[XOnIEmgZYZ1\XJiMjDodpMh[nliaX3teY5weHKnY3nwbZRifGmxbjDhd5NigSxiRVO1NEA:KDBwMEO0JO69VS5? MmjCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{MUiyOlQoRjJ4MkG4NlY1RC:jPh?=
SKOV3 NGnld5dIem:5dHigbY5pcWKrdHnvckBie3OjeR?= M{nLT|Qh\GG7cx?= M1[5[2dzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJHNMV1Z|IHPlcIx{KGGodHXyJFQh\GG7czDifUBYW1R6IHHzd4F6NCCLQ{WwJF0hOC5zNEKg{txONg>? M1Xnc|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzNESzNlMzLz5{MUS0N|I{OjxxYU6=
MDA-MB-231 NIjMXJRIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MmO0OEBl[Xm| NGXofYRIem:5dHigbY5pcWKrdHnvckBw\iCqdX3hckBOTEFvTVKtNlMyKGOnbHzzJIFnfGW{IESg[IF6eyCkeTDXV3Q5KGG|c3H5MEBKSzVyIE2gNE4yPDRizszNMi=> Moe5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF2NEOyN|IoRjJzNESzNlMzRC:jPh?=
MDA-MB-231 M4[1[2Z2dmO2aX;uJIF{e2G7 MXGxNEBvVQ>? NIX5dXpKdmS3Y4Tpc44hd2ZiZHXndoFl[XSrb36gc4Yh[0mDUEGgbY4hcHWvYX6gUWRCNU2ELUKzNUBk\WyuczDheEAyOCCwTTDifUBY\XO2ZYLuJIJtd3RiYX7hcJl{cXN? NGLUVmk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUS0N|I{Oid-MkG0OFMzOzJ:L3G+
MDA-MB-231 NInVPHlHfW6ldHnvckBie3OjeR?= Mn3KNVAxKG6P NV3uVmFEOTVibXnudy=> NUToe5l3UW6mdXP0bY9vKG:oIHTl[5Ji\GG2aX;uJI9nKGOLQWCxJIlvKGi3bXHuJG1FSS2PQj2yN|Eh[2WubIOgZZQhOTByIH7NJIFnfGW{IEG1JI1qdnNiYomgW4V{fGW{bjDicI91KGGwYXz5d4l{ M4nUdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzNESzNlMzLz5{MUS0N|I{OjxxYU6=
MDA-MB-231 MUTBdI9xfG:|aYOgZZN{[Xl? M2TIdFEvPSC3TR?= M1;MVVEzKGi{cx?= NWDvWVR4UW6mdXP0bY9vKG:oIHHwc5B1d3OrczDpckBpfW2jbjDNSGEuVUJvMkOxJINmdGy|IHHzd4V{e2WmIHHzJIFkfGm4YYTpc44hd2ZiY3HzdIF{\S1|IHHjeIl3cXS7IHH0JFEvPSC3TTDh[pRmeiBzMjDodpMh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nz M3HQWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzNESzNlMzLz5{MUS0N|I{OjxxYU6=
MDA-MB-231 M2nPO2Fxd3C2b4Ppd{Bie3OjeR?= NGjjVIgyNjVidV2= NH7RbIIyOiCqcoO= NUjTUo1YUW6mdXP0bY9vKG:oIHHwc5B1d3OrczDpckBpfW2jbjDNSGEuVUJvMkOxJINmdGy|IHHzd4V{e2WmIHHzJIFkfGm4YYTpc44hd2ZiUFHSVEBkdGWjdnHn[UBifCBzLkWgeW0h[W[2ZYKgNVIhcHK|IHL5JHdme3Sncn6gZoxwfCCjbnHsfZNqew>? NU\1[HU4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG0OFMzOzJpPkKxOFQ{OjN{PD;hQi=>
MDA-MB-231 NH;pdINCdnSrdIXtc5Ih[XO|YYm= M3rhXVMxKG2pL3vn NWmzNYVnOiC5ZXXrdy=> NVTQT2xuSW62aYT1cY9zKGGldHn2bZR6KGGpYXnud5QhcHWvYX6gUWRCNU2ELUKzNUBk\WyuczD4[Y5w\3KjZoTl[EBqdiCVQ1nEJI1wfXOnIHHzd4V{e2WmIHnubIljcXSrb36gc4YhfHWvb4Kg[5Jwf3SqIHH0JFMxKG2pL3vnMEBxdyCjZH3pcol{fGW{ZXSg[IFqdHliZn;yJFUh\GG7cz;3[YVsKG[xcjCyJJdm\Wu| NIrCU5M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUS0N|I{Oid-MkG0OFMzOzJ:L3G+
MDA-MB-231 MXLBcpRqfHWvb4KgZZN{[Xl? MY[xNFAhdWdxa3e= NEfMRmIzKHenZXvz M1zBb2FvfGm2dX3vdkBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3ERU1OSi1{M{GgZ4VtdHNieHXuc4dz[W[2ZXSgbY4hW0OLRDDtc5V{\SCjc4Pld5Nm\CCrbnjpZol1cW:wIH;mJJR2dW:{IHfyc5d1cCCjdDCxNFAhdWdxa3esJJBwKGGmbXnubZN1\XKnZDDkZYltgSCob4KgOUBl[Xm|L4fl[Ysh\m:{IEKge4Vmc3N? NHPwflE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUS0N|I{Oid-MkG0OFMzOzJ:L3G+
MDA-MB-231 M4XsSmFvfGm2dX3vdkBie3OjeR?= NX71S2FTOTByIH3nM4to NUG0OHZ{\X[ncomgN{Bl[Xm| M3vIUmFvfGm2dX3vdkBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3ERU1OSi1{M{GgZ4VtdHNieHXuc4dz[W[2ZXSgbY4hSmGuYj;jJHNEUURibX;1d4Uh[XO|ZYPz[YQh[XNidIXtc5Ih\3Kxd4ToJIlvcGmkaYTpc44h[XRiMUCwJI1oN2upLDDwc{By\CCvZXHzeZJm\CCndnXyfUA{KGSjeYO= MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjJzOEK2OEc,OjZ{MUiyOlQ9N2F-
DAOY NY\FWWpPeUiWUzDhd5NigQ>? NIjWdG5yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiRFHPXUBk\Wyucx?= Mly3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
SJ-GBM2 MVXxTHRUKGG|c3H5 MkjGdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKFOMLVfCUVIh[2WubIO= M37uPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
A673 NX[0cXdQeUiWUzDhd5NigQ>? NXXSc3JleUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFG2O|Mh[2WubIO= M{m4TVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-MC MYnxTHRUKGG|c3H5 M1XwOpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMW1EKGOnbHzz NYrNRo5WRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
BT-37 NHfqfpVyUFSVIHHzd4F6 MUjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSlRvM{egZ4VtdHN? NGDSb|U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
NB-EBc1 NVrYNHBqeUiWUzDhd5NigQ>? M{\0XZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCQQj3FRoMyKGOnbHzz NFvXSFc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
Saos-2 MmfvdWhVWyCjc4PhfS=> NUP3N5pVeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPhc5MuOiClZXzsdy=> NGHkSJQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
LAN-5 MlHmdWhVWyCjc4PhfS=> NHHzWldyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTFHOMVUh[2WubIO= MmXuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
BT-12 MYfxTHRUKGG|c3H5 NVzlVXVXeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFLUMVEzKGOnbHzz M3rNSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
OHS-50 MoHsdWhVWyCjc4PhfS=> MUHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhV0iVLUWwJINmdGy| NF;qPY09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
SK-N-MC M331SpFJXFNiYYPzZZk> MYHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDTT{1PNU2FIHPlcIx{ NGP0c3Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
TC32 NYDZUFFxeUiWUzDhd5NigQ>? MYjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDUR|MzKGOnbHzz MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
Assay
Methods Test Index PMID
Western blot cIAP-1 / XIAP / Mcl-1 / pS6K1 / Cleaved PARP 28036295
Growth inhibition assay Cell viability 28036295
In vivo AT-406 has good pharmacokinetic (PK) properties and oral bioavailability in mice, rats, non-human primates, and dogs. In the MDA-MB-231 xenograft, AT-406 effectively induces cIAP1 degradation and processing of procaspase-8, cleavage of PARP in tumor tissues at 100 mg/kg with well toleration even at 200 mg/kg. AT-406 induces significant tumor growth inhibition with p of 0.0012 at 100 mg/kg. [1]

Protocol (from reference)

Kinase Assay:

[1]

  • Fluorescence Polarization Based Assays for XIAP, cIAP1, and cIAP2 BIR3 Proteins:

    FL-AT-406 (the fluorescently tagged AT-406) is employed to develop a set of new FP assays for determination of the binding affinities of Smac mimetics to XIAP, cIAP-1, and cIAP-2 BIR3 proteins. The Kd value of FL-AT-406 to each IAP protein is determined by titration experiments using a fixed concentration of FL-AT-406 and different concentrations of the protein up to full saturation. Fluorescence polarization values are measured using an Infinite M-1000 plate reader in Microfluor 2 96-well, black, round-bottom plates. To each well, FL-AT-406 (2, 1, and 1 nM for experiments with XIAP BIR3, cIAP-1 BIR3, and cIAP-2 BIR3, respectively) and different concentrations of the protein are added to a final volume of 125 μL in the assay buffer (100 mM potassium phosphate, pH 7.5, 100 μg/mL bovine γ-globulin, 0.02% sodium azide, with 4% DMSO). Plates are mixed and incubated at room temperature for 2-3 hours with gentle shaking. The polarization values in millipolarization units (mP) are measured at an excitation wavelength of 485 nm and an emission wavelength of 530 nm. Equilibrium dissociation constants (Kd) are then calculated by fitting the sigmoidal dose-dependent FP increases as a function of protein concentrations using Graphpad Prism 5.0 software. In competitive binding experiments for XIAP3 BIR3, AT-406 is incubated with 20 nM XIAP BIR3 protein and 2 nM FL-AT-406 in the assay buffer (100 mM potassium phosphate, pH 7.5; 100 μg/mL bovine γ-globulin; 0.02% sodium azide). In competitive binding experiments for cIAP1 BIR3 protein, 3 nM protein and 1 nM FL-AT-406 are used. In competitive binding experiments for cIAP2 BIR3, 5 nM protein and 1 nM FL-AT-406 are used. For each competitive binding experiment, polarization values are measured after 2-3 hours of incubation using an Infinite M-1000 plate reader. The IC50 value, the inhibitor concentration at which 50% of the bound tracer is displaced, is determined from the plot using nonlinear least-squares analysis. Curve fitting is performed using the PRISM software. A Ki value for AT-406 is calculated.

Cell Research:

[1]

  • Cell lines: MDA-MB-231 breast cancer and SK-OV-3 ovarian cancer cell lines
  • Concentrations: ~ 1 μM
  • Incubation Time: 4 days
  • Method:

    Cells are seeded in 96-well flat bottom cell culture plates at a density of (3-4) × 103 cells/well with AT-406 and incubated for 4 days. The rate of cell growth inhibition after treatment with different concentrations of AT-406 is determined by assaying with (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt (WST-8). WST-8 is added to each well to a final concentration of 10%, and then the plates are incubated at 37 °C for 2−3 hours. The absorbance of the samples is measured at 450 nm using a TECAN ULTRA reader. Concentration of AT-406 that inhibited cell growth by 50% (IC50) is calculated by comparing absorbance in the untreated cells and the cells treated with AT-406.

Animal Research:

[1]

  • Animal Models: MDA-MB-231 xenograft tumors in severe combined immune deficiency (SCID) mice
  • Dosages: 10 mg/kg (i.v.), 10 mg/kg (p.o.), 30 mg/kg (p.o.) and 100 mg/kg (p.o.)
  • Administration: Administered via intravenously (i.v.) or oral gavage (p.o.)

Solubility (25°C)

In vitro

DMSO 100 mg/mL
(178.02 mM)
Water Insoluble
Ethanol '100 mg/mL

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
30% propylene glycol, 5% Tween 80, 65% D5W
For best results, use promptly after mixing.

30 mg/mL

Chemical Information

Molecular Weight 561.71
Formula

C32H43N5O4

CAS No. 1071992-99-8
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC(C)CC(=O)N1CCC2CCC(N2C(=O)C(C1)NC(=O)C(C)NC)C(=O)NC(C3=CC=CC=C3)C4=CC=CC=C4

In vivo Formulation Calculator (Clear solution)

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

mg/kg g μL

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

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT01265199 Terminated Drug: AT-406 in combination with daunorubicin and cytarabine Acute Myelogenous Leukemia (AML) Ascenta Therapeutics|The Leukemia and Lymphoma Society February 2011 Phase 1
NCT01078649 Completed Drug: Debio 1143 (AT-406) Cancer|Solid Tumors|Lymphoma|Malignancy Debiopharm International SA March 29 2010 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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

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