TG101209

Name: TG101209
Brand: Selleck Chemicals
SKU: S2692
Rating: 5 (7 reviews)

For research use only. Not for use in humans.

Catalog No.S2692

7 publications

Molecular Weight(MW): 509.67

TG101209 is a selective JAK2 inhibitor with IC50 of 6 nM, less potent to Flt3 and RET with IC50 of 25 nM and 17 nM in cell-free assays, ~30-fold selective for JAK2 than JAK3, sensitive to JAK2V617F and MPLW515L/K mutations.

Selleck's TG101209 has been cited by 7 publications

Nat Commun, 2018, 9(1):3259

PubMed: 30108215 ( click the link to review the publication )

Int Immunopharmacol, 2018, 54:354-365

PubMed: 29202299 ( click the link to review the publication )

Nat Commun, 2017, 8(1):1130

PubMed: 29066712 ( click the link to review the publication )

Oncotarget, 2017, 8(63):106753-106763

PubMed: 29290986 ( click the link to review the publication )

Leukemia, 2014, 28(7):1519-28

PubMed: 24402161 ( click the link to review the publication )

ACS Chem Biol, 2014, 9(5):1160-71

PubMed: 24568369 ( click the link to review the publication )

Cancer Lett, 2013, 341(2):224-30

PubMed: 23941832 ( click the link to review the publication )

3 Customer Reviews

EGFR-ERCC1 effect on survival. QGP1 cells were transfected with Scrambled, ERCC1, EGFR, or EGFR-ERCC1 siRNA. Following 48 hours of siRNA transfection, Scrambled siRNA and ERCC1 siRNA-transfected cells were treated with 1 umol/L gefitinib or 125 nmol/L NU7026 (DNAPK inhibitor), or both, while EGFR siRNA and EGFR-ERCC1 siRNA-transfected cells were treated with 125 nmol/L of NU7026 1 hour prior 4 Gy IR treatment. Survival of these cells was then assessed 72 hours following IR treatment via MTT assay. The graphs show percentage of survival from 3 independent experiments as compared with untreated control. Bars show SD. Asterisks show statistical significance (*,P < 0.05; **, P < 0.01; ***, P < 0.001; NS, nonsignificant).

Clin Cancer Res 2014 20(13), 3496-506. TG101209 purchased from Selleck.

Primary plasma cells from MM patient 5 used were incubated with indicated concentrations of LCL161, TG101209 or the combination for 24 h. Western blot analysis were performed to examine expression levels of pStat3 and IAPs.

Leukemia 2014 28(7), 1519-28. TG101209 purchased from Selleck.
Claude HAAN Université du Luxembour. TG101209 purchased from Selleck.

Purity & Quality Control

Choose Selective JAK Inhibitors

Biological Activity

Description

Targets

JAK2 ^[1] (Cell-free assay)	RET ^[1] (Cell-free assay)	FLT3 ^[1] (Cell-free assay)	JAK3 ^[1] (Cell-free assay)
6 nM	17 nM	25 nM	169 nM

In vitro

TG101209 is an orally bioavailable, small molecule, ATP-competitive inhibitor towards several tyrosine kinases. TG101209 inhibits growth of Ba/F3 cells expressing JAK2V617F or MPLW515L mutations with an IC50 of B200 nM. In a human JAK2V617F-expressing acute myeloid leukemia cell line, TG101209 inducs cell cycle arrest and apoptosis, and inhibits phosphorylation of JAK2V617F, STAT5 and STAT3. TG101209 suppresses growth of hematopoietic colonies from primary progenitor cells harboring JAK2V617F or MPL515 mutations. ^[1] TG101209 significantly reduces STAT5 phosphorylation without affecting the total amount of STAT5 protein. ^[2] TG101209 inhibits survivin and reduces phosphorylation of STAT3 in HCC2429 and H460 lung cancer cells. TG101209 results in radio sensitization of HCC2429 and H460 lung cancer cells in vitro. ^[3] A recent study indicates TG101209 abrogates BCR-JAK2 and STAT5 phosphorylation, decreases Bcl-xL expression and triggered apoptosis of transformed Ba/F3 cells. ^[4]

In vivo

100 mg/kg of TG101209 effectively prolongs the survival in JAK2V617F-induced disease (10 days). Compared with placebo-treated animals, TG101209-treated animals exhibit statistically significant, dose-dependent reduction in the circulating tumor cell burden at day +11 to 20%. ^[1]

Protocol

Kinase Assay:^[1]	- Collapse Cell-free Kinase Activity Assays: IC50 values for TG101209 are determined using a luminescence-based kinase assay with recombinant JAK2, VEGFR2/KDR, and JAK3 obtained from Upstate Cell Signaling Solutions. Kinase reactions are carried out in a buffer consisting of 40mM Tris buffer (pH 7.4), 50mM MgCl₂, 800M EGTA, 350M Triton X-100, 2M -mercaptoethanol, 100M peptide substrate, and an appropriate amount of JAK2, VEGFR2/KDR or JAK3 such that the assay is linear over 60 minutes. The reaction is initiated by the addition of 10L of ATP to a final concentration of 3mM and terminated by the addition of Kinase-Glo reagent after 60 minutes. Luciferase activity is quantified using an Ultra 384 instrument set for luminosity measurements. IC50 values are derived from experimental data using the non-linear curve fitting capabilities of the GraphPad Prism 4.0 software. The single concentration inhibition data for a panel of 63 kinases is determined using the SelectScreen ^TM service.
Cell Research:^[1]	- Collapse Cell lines: Ba/F3 cells expressing JAK2V617F (Ba/F3-EpoR-V617F) and MPLW515L (Ba/F3-W515L) mutants. Concentrations: 4.6-38 400 nM Incubation Time: 28-30 hours Method: In brief, approximately 2 × 10³ cells are plated into microtiterplate wells in 100 ml RPMI-1640 growth media with indicated concentrations of TG101209. The relative growth of cells is quantified at 24-hour intervals using Cell Proliferation Kit II (XTT) as per manufacturer's guidelines. After incubation, 20 mL of XTT is added to the wells and allowed to incubate for 4-6 hours. The colored formazan product is measured spectrophotometrically at 450 nm with correction at 650 nm, and IC50 values are determined using the GraphPad Prism 4.0 software. Data are subjected to a non-linear regression-fit analysis and IC50 values are determined as the concentration that inhibited proliferation by 50%. All experiments are done in triplicate and the results normalized to growth of untreated cells. (Only for Reference)
Animal Research:^[1]	- Collapse Animal Models: Ba/F3-V617F-GFP cells are injected into immunodeficient SCID mice to induce a rapidly fatal, fully penetrant hematopoietic disease. Formulation: TG101209 is dissolved in DMSO. Dosages: 100 mg/kg Administration: TG101209 is administered via oral gavage at the indicated doses beginning day +3 after tumor cell infusion and ending on day +20. (Only for Reference)

References

- Collapse

Solubility (25°C)

In vitro	DMSO	102 mg/mL (200.12 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 1% DMSO+30% polyethylene glycol+1% Tween 80 For best results, use promptly after mixing.	12 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download TG101209 SDF

Molecular Weight	509.67
Formula	C₂₆H₃₅N₇O₂S
CAS No.	936091-14-4
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	N/A
Smiles	CN1CCN(CC1)C2=CC=C(NC3=NC=C(C)C(=N3)NC4=CC(=CC=C4)[S](=O)(=O)NC(C)(C)C)C=C2

Bio Calculators

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration _(start) x Volume _(start) = Concentration _(final) x Volume _(final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

Serial Dilutions
Concertration (start):
Dilution-folds:

Computed Result

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):

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

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.

JAK Signaling Pathway Map

JAK Inhibitors with Unique Features

Pan JAK Inhibitor

Ruxolitinib (INCB018424) : Pan JAK1/2 inhibitor, IC50=3.3 nM/2.8 nM.
Most Potent JAK Inhibitor

AZD1480 : JAK2, IC50=0.26 nM.
FDA-approved JAK Inhibitor

Tofacitinib (CP-690550,Tasocitinib) : Approved by FDA for rheumatoid arthritis (RA).
Newest JAK Inhibitor

Pacritinib (SB1518) ^New : Potent and selective inhibitor of Janus Kinase 2 (JAK2) and Fms-Like Tyrosine Kinase-3 (FLT3) with IC50s of 23 and 22 nM, respectively.

Related JAK Products

FLLL32 ^New

FLLL32 is a potent JAK2/STAT3 inhibitor with IC50 of <5 μM.
Cerdulatinib (PRT062070) ^New

Cerdulatinib (PRT-062070) is an oral active, multi-targeted tyrosine kinase inhibitor with IC50 of 12 nM/6 nM/8 nM/0.5 nM and 32 nM for JAK1/JAK2/JAK3/TYK2 and Syk, respectively. Also inhibits 19 other tested kinases with IC50 less than 200 nM.
Ruxolitinib (INCB018424)

Ruxolitinib (INCB018424) is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3.
Tofacitinib (CP-690550) Citrate

Tofacitinib citrate (CP-690550 citrate) is a novel inhibitor of JAK with IC50 of 1 nM, 20 nM and 112 nM against JAK3, JAK2, and JAK1, respectively.
Tofacitinib (CP-690550)

Tofacitinib (CP-690550,Tasocitinib) is a novel inhibitor of JAK3 with IC50 of 1 nM in cell-free assays, 20- to 100-fold less potent against JAK2 and JAK1.
AZD1480

AZD1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM in a cell-free assay, selectivity against JAK3 and Tyk2, and to a smaller extent against JAK1. Phase 1.
Fedratinib (TG101348)

Fedratinib (SAR302503, TG101348) is a selective inhibitor of JAK2 with IC50 of 3 nM in cell-free assays, 35- and 334-fold more selective for JAK2 versus JAK1 and JAK3. Phase 2.
Momelotinib (CYT387)

Momelotinib (CYT387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, ~10-fold selectivity versus JAK3. Phase 3.
WP1066

WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3. Phase 1.

Features:Similar to its parent compound AG490, WP1066 inhibits the phosphorylation of JAK2, but unlike AG490, WP1066 also degraded JAK2 protein.

Choose Your Country or Region

By Signaling Pathways

By product type

TG101209