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MedKoo Cat#: 406190 | Name: TG101209
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

TG101209 is a novel and potent JAK2 inhibitor, which induced dose- and time-dependent cytotoxicity in a variety of multiple myeloma (MM) cell lines. The induction of cytotoxicity was associated with inhibition of cell cycle progression and induction of apoptosis in myeloma cell lines and patient-derived plasma cells. Exploring the mechanism of action of TG101209 indicated downregulation of pJak2, pStat3, and Bcl-xl levels with upregulation of pErk and pAkt levels indicating cross talk between signaling pathways. TG101209 , when used in combination with the PI3K inhibitor LY294002, demonstrated synergistic cytotoxicity against myeloma cells.

Chemical Structure

TG101209
TG101209
CAS#936091-14-4

Theoretical Analysis

MedKoo Cat#: 406190

Name: TG101209

CAS#: 936091-14-4

Chemical Formula: C26H35N7O2S

Exact Mass: 509.2573

Molecular Weight: 509.67

Elemental Analysis: C, 61.27; H, 6.92; N, 19.24; O, 6.28; S, 6.29

Price and Availability

Size Price Availability Quantity
10mg USD 90.00 Ready to ship
25mg USD 150.00 Ready to ship
50mg USD 250.00 Ready to ship
100mg USD 450.00 Ready to ship
200mg USD 750.00 Ready to ship
500mg USD 1,650.00 Ready to ship
1g USD 2,950.00 Ready to ship
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Related CAS #
No Data
Synonym
TG101209; TG-101209; TG 101209
IUPAC/Chemical Name
N-tert-butyl-3-(5-methyl-2-(4-(4-methylpiperazin-1-yl)phenylamino)pyrimidin-4-ylamino)benzenesulfonamide
InChi Key
JVDOKQYTTYUYDV-UHFFFAOYSA-N
InChi Code
InChI=1S/C26H35N7O2S/c1-19-18-27-25(29-20-9-11-22(12-10-20)33-15-13-32(5)14-16-33)30-24(19)28-21-7-6-8-23(17-21)36(34,35)31-26(2,3)4/h6-12,17-18,31H,13-16H2,1-5H3,(H2,27,28,29,30)
SMILES Code
O=S(C1=CC=CC(NC2=NC(NC3=CC=C(N4CCN(C)CC4)C=C3)=NC=C2C)=C1)(NC(C)(C)C)=O
Appearance
white solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
        
Biological target:
TG101209 is a JAK2 inhibitor with IC50 of 6 nM.
In vitro activity:
The DU 528, HSD2, PEER, MOLT-4 and Jurkat T-ALL cell lines were treated with TG101209, and cell proliferation was analysed using MTT assay. The IC50s of the cell lines were 2.542 µM (DU528), 0.329 µM (HSD2), 0.612 µM (PEER), 2.893 µM (MOLT-4) and 1.794 µM (Jurkat) (Supplementary Figure 2). Apoptosis was increased in the HSD2 and PEER cell lines in a TG101209 concentration-dependent manner, according to the flow cytometry analysis. The expression of apoptosis-related proteins (Bax, Cleaved PARP, caspase-3 and caspase-9) was determined by Western blotting. The expression levels of Bax and Cleaved PARP were up-regulated by TG101209, while caspase-3 and caspase-9 were down-regulated in both HSD2 and PEER cell lines (Figure 3A). The cell cycle of each cell line was analysed using flow cytometry. After treatment, the cell cycle was arrested mainly at the G2/M phase. The expression of the indicated cell cycle-related proteins (P21, P27, CDK4 and CDK6) was determined by Western blotting. The expression levels of P21 and P27 were up-regulated by TG101209, while those of CDK4 and CDK6 were down-regulated by TG101209 in both the HSD2 and PEER cell lines (Figure 3B). Primary bone marrow cells from T-ALL patients and healthy controls were treated with TG101209 (0, 1, 2, 4, 6, 8, or 10 μM), and cell proliferation was analysed using MTT assay. The IC50s were 0.755um and 1.565 um respectively. (Supplementary Figure 2). Apoptosis was increased in the cells in a TG101209 concentration-dependent manner, according to the flow cytometry analysis. (Figure 3A). Reference: Oncotarget. 2017 Oct 23;8(63):106753-106763. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739771/
In vivo activity:
To test the in vivo efficacy of TG101209 in inhibiting JAK2V617F, a mouse model of JAK2V617F-induced hematopoietic disease was used. All the animals in the control group died due to disease progression by day 11. In striking contrast, TG101209 at the highest dose level (100 mg/kg b.i.d.) was effective in treating JAK2V617F-induced disease as there was a statistically significant prolongation of survival in this group (10 days; P<0.02), and the animals in this group were still alive at the previously defined study end point of 10 days past the time of death of the final placebo-treated animal (Figure 6a). The animals at the lower dose levels (that is, 10 or 30 mg/kg b.i.d.) developed disease with the same latency and penetrance as the placebo-treated animals, without evidence of prolongation of survival (Figure 6a). Compared with placebo-treated animals, TG101209-treated animals exhibited a statistically significant, dose-dependent reduction in the circulating tumor cell burden at day +11 (75% GFP+ cells in placebo-treated versus 15% GFP+ cells in 100 mg/kg b.i.d. TG101209-treated animals; P<0.02) (Figure 6b). The clinical benefit of TG101209 in this model correlated with inhibition of JAK2V617F activity in vivo, evident in the marked decrease in STAT-5 phosphorylation demonstrable in splenic tumors, as early as 7 h after administration of a single dose of TG101209 (100 mg/kg) to the affected mice (Figure 6c). Reference: Leukemia. 2007 Aug;21(8):1658-68. https://www.nature.com/articles/2404750
Solvent mg/mL mM
Solubility
DMSO 29.2 57.23
DMF 16.0 31.39
DMF:PBS (pH 7.2) (1:1) 0.5 0.98
Ethanol 0.1 0.24
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 509.67 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Ramakrishnan V, Kimlinger T, Haug J, Timm M, Wellik L, Halling T, Pardanani A, Tefferi A, Rajkumar SV, Kumar S. TG101209, a novel JAK2 inhibitor, has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD45+ myeloma cells. Am J Hematol. 2010 Sep;85(9):675-86. doi: 10.1002/ajh.21785. PMID: 20652971; PMCID: PMC2940994. 2. Cheng Z, Yi Y, Xie S, Yu H, Peng H, Zhang G. The effect of the JAK2 inhibitor TG101209 against T cell acute lymphoblastic leukemia (T-ALL) is mediated by inhibition of JAK-STAT signaling and activation of the crosstalk between apoptosis and autophagy signaling. Oncotarget. 2017 Oct 23;8(63):106753-106763. doi: 10.18632/oncotarget.22053. PMID: 29290986; PMCID: PMC5739771. 3. Pardanani A, Hood J, Lasho T, Levine RL, Martin MB, Noronha G, Finke C, Mak CC, Mesa R, Zhu H, Soll R, Gilliland DG, Tefferi A. TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations. Leukemia. 2007 Aug;21(8):1658-68. doi: 10.1038/sj.leu.2404750. Epub 2007 May 31. PMID: 17541402. 4. Sun Y, Moretti L, Giacalone NJ, Schleicher S, Speirs CK, Carbone DP, Lu B. Inhibition of JAK2 signaling by TG101209 enhances radiotherapy in lung cancer models. J Thorac Oncol. 2011 Apr;6(4):699-706. doi: 10.1097/JTO.0b013e31820d9d11. PMID: 21325979; PMCID: PMC3104103.
In vitro protocol:
1. Ramakrishnan V, Kimlinger T, Haug J, Timm M, Wellik L, Halling T, Pardanani A, Tefferi A, Rajkumar SV, Kumar S. TG101209, a novel JAK2 inhibitor, has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD45+ myeloma cells. Am J Hematol. 2010 Sep;85(9):675-86. doi: 10.1002/ajh.21785. PMID: 20652971; PMCID: PMC2940994. 2. Cheng Z, Yi Y, Xie S, Yu H, Peng H, Zhang G. The effect of the JAK2 inhibitor TG101209 against T cell acute lymphoblastic leukemia (T-ALL) is mediated by inhibition of JAK-STAT signaling and activation of the crosstalk between apoptosis and autophagy signaling. Oncotarget. 2017 Oct 23;8(63):106753-106763. doi: 10.18632/oncotarget.22053. PMID: 29290986; PMCID: PMC5739771.
In vivo protocol:
1. Pardanani A, Hood J, Lasho T, Levine RL, Martin MB, Noronha G, Finke C, Mak CC, Mesa R, Zhu H, Soll R, Gilliland DG, Tefferi A. TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations. Leukemia. 2007 Aug;21(8):1658-68. doi: 10.1038/sj.leu.2404750. Epub 2007 May 31. PMID: 17541402. 2. Sun Y, Moretti L, Giacalone NJ, Schleicher S, Speirs CK, Carbone DP, Lu B. Inhibition of JAK2 signaling by TG101209 enhances radiotherapy in lung cancer models. J Thorac Oncol. 2011 Apr;6(4):699-706. doi: 10.1097/JTO.0b013e31820d9d11. PMID: 21325979; PMCID: PMC3104103.
1: Bouzian Y, El Hafi M, Parvizi N, Kim W, Subaşioğlu M, Ozcan M, Turkez H, Mardinoglu A. Design and evaluation of novel inhibitors for the treatment of clear cell renal cell carcinoma. Bioorg Chem. 2024 Oct;151:107597. doi: 10.1016/j.bioorg.2024.107597. Epub 2024 Jul 6. PMID: 39002511. 2: Spriano F, Sartori G, Tarantelli C, Barreca M, Golino G, Rinaldi A, Napoli S, Mascia M, Scalise L, Arribas AJ, Cascione L, Zucca E, Stathis A, Gaudio E, Bertoni F. Pharmacologic screen identifies active combinations with BET inhibitors and LRRK2 as a novel putative target in lymphoma. EJHaem. 2022 Jul 27;3(3):764-774. doi: 10.1002/jha2.535. PMID: 36051080; PMCID: PMC9422027. 3: Yan B, Liu P, Yi X, Li J, Liu N, Zhu W, Kuang Y, Chen X, Peng C. Topical VX-509 attenuates psoriatic inflammation through the STAT3/FABP5 pathway in keratinocytes. Pharmacol Res. 2022 Aug;182:106318. doi: 10.1016/j.phrs.2022.106318. Epub 2022 Jun 18. PMID: 35728766. 4: Moteki H, Ogihara M, Kimura M. Cell proliferation effects of S-allyl-L- cysteine are associated with phosphorylation of janus kinase 2, insulin-like growth factor type-I receptor tyrosine kinase, and extracellular signal- regulated kinase 2 in primary cultures of adult rat hepatocytes. Eur J Pharmacol. 2022 Jul 15;927:175067. doi: 10.1016/j.ejphar.2022.175067. Epub 2022 May 30. PMID: 35654135. 5: Moteki H, Ogihara M, Kimura M. S-Allyl-L-cysteine Promotes Cell Proliferation by Stimulating Growth Hormone Receptor/Janus Kinase 2/Phospholipase C Pathways and Promoting Insulin-Like Growth Factor Type-I Secretion in Primary Cultures of Adult Rat Hepatocytes. Biol Pharm Bull. 2022;45(5):625-634. doi: 10.1248/bpb.b21-01071. PMID: 35491167. 6: Li X, Shong K, Kim W, Yuan M, Yang H, Sato Y, Kume H, Ogawa S, Turkez H, Shoaie S, Boren J, Nielsen J, Uhlen M, Zhang C, Mardinoglu A. Prediction of drug candidates for clear cell renal cell carcinoma using a systems biology-based drug repositioning approach. EBioMedicine. 2022 Apr;78:103963. doi: 10.1016/j.ebiom.2022.103963. Epub 2022 Mar 25. PMID: 35339898; PMCID: PMC8960981. 7: Zhang Y, Li J, Zhong H, Xiao X, Wang Z, Cheng Z, Hu C, Zhang G, Liu S. The JAK2 inhibitor TG101209 exhibits anti-tumor and chemotherapeutic sensitizing effects on Burkitt lymphoma cells by inhibiting the JAK2/STAT3/c-MYB signaling axis. Cell Death Discov. 2021 Sep 29;7(1):268. doi: 10.1038/s41420-021-00655-1. PMID: 34588425; PMCID: PMC8481535. 8: Gong K, Song K, Zhu Z, Xiang Q, Wang K, Shi J. SWIM domain protein ZSWIM4 is required for JAK2 inhibition resistance in breast cancer. Life Sci. 2021 Aug 15;279:119696. doi: 10.1016/j.lfs.2021.119696. Epub 2021 Jun 5. PMID: 34102191. 9: Kimura M, Kurihara K, Moteki H, Ogihara M. Growth Hormone Signaling Pathway Leading to the Induction of DNA Synthesis and Proliferation in Primary Cultured Hepatocytes of Adult Rats. J Pharm Pharm Sci. 2021;24:1-15. doi: 10.18433/jpps31586. PMID: 33434118. 10: Kurihara K, Moteki H, Kimura M, Ogihara M. Autocrine secretion of insulin- like growth factor-I mediates growth hormone-stimulated DNA synthesis and proliferation in primary cultures of adult rat hepatocytes. Eur J Pharmacol. 2021 Jan 15;891:173753. doi: 10.1016/j.ejphar.2020.173753. Epub 2020 Nov 25. PMID: 33245901. 11: Kim JH, Choi HS, Kim SL, Lee DS. The PAK1-Stat3 Signaling Pathway Activates IL-6 Gene Transcription and Human Breast Cancer Stem Cell Formation. Cancers (Basel). 2019 Oct 10;11(10):1527. doi: 10.3390/cancers11101527. PMID: 31658701; PMCID: PMC6826853. 12: Toh TB, Lim JJ, Hooi L, Rashid MBMA, Chow EK. Targeting Jak/Stat pathway as a therapeutic strategy against SP/CD44+ tumorigenic cells in Akt/β-catenin- driven hepatocellular carcinoma. J Hepatol. 2020 Jan;72(1):104-118. doi: 10.1016/j.jhep.2019.08.035. Epub 2019 Sep 18. PMID: 31541681. 13: Cheng Z, Yi Y, Xie S, Yu H, Peng H, Zhang G. The effect of the JAK2 inhibitor TG101209 against T cell acute lymphoblastic leukemia (T-ALL) is mediated by inhibition of JAK-STAT signaling and activation of the crosstalk between apoptosis and autophagy signaling. Oncotarget. 2017 Oct 23;8(63):106753-106763. doi: 10.18632/oncotarget.22053. PMID: 29290986; PMCID: PMC5739771. 14: Hu J, Wang Y, Li Y, Xu L, Cao D, Song S, Damaneh MS, Wang X, Meng T, Chen YL, Shen J, Miao Z, Xiong B. Discovery of a series of dihydroquinoxalin-2(1H)-ones as selective BET inhibitors from a dual PLK1-BRD4 inhibitor. Eur J Med Chem. 2017 Sep 8;137:176-195. doi: 10.1016/j.ejmech.2017.05.049. Epub 2017 May 27. PMID: 28586718. 15: Zhang Y, Liang R, Chen CW, Mallano T, Dees C, Distler A, Reich A, Bergmann C, Ramming A, Gelse K, Mielenz D, Distler O, Schett G, Distler JHW. JAK1-dependent transphosphorylation of JAK2 limits the antifibrotic effects of selective JAK2 inhibitors on long-term treatment. Ann Rheum Dis. 2017 Aug;76(8):1467-1475. doi: 10.1136/annrheumdis-2016-210911. Epub 2017 May 6. PMID: 28478401. 16: Demyanets S, Jaeger E, Pablik E, Greiner G, Herndlhofer S, Valent P, Schwarzinger I. The JAK2 blocker TG101209 is a potent inhibitor of clonogenic progenitor cell growth in patients with chronic myeloid leukaemia. Br J Haematol. 2018 Apr;181(1):137-139. doi: 10.1111/bjh.14508. Epub 2017 Feb 21. PMID: 28220937. 17: Chakraborty SN, Leng X, Perazzona B, Sun X, Lin YH, Arlinghaus RB. Combination of JAK2 and HSP90 inhibitors: an effective therapeutic option in drug-resistant chronic myelogenous leukemia. Genes Cancer. 2016 May;7(5-6):201-208. doi: 10.18632/genesandcancer.111. PMID: 27551334; PMCID: PMC4979592. 18: Geissler K, Jäger E, Barna A, Sliwa T, Knöbl P, Schwarzinger I, Gisslinger H, Valent P. In vitro and in vivo effects of JAK2 inhibition in chronic myelomonocytic leukemia. Eur J Haematol. 2016 Dec;97(6):562-567. doi: 10.1111/ejh.12773. Epub 2016 Jun 15. PMID: 27157043. 19: Mu C, Wu X, Ma H, Tao W, Zhang G, Xia X, Shen J, Mai J, Sun T, Sun X, Arlinghaus RB, Shen H. Effective Concentration of a Multikinase Inhibitor within Bone Marrow Correlates with In Vitro Cell Killing in Therapy-Resistant Chronic Myeloid Leukemia. Mol Cancer Ther. 2016 May;15(5):899-910. doi: 10.1158/1535-7163.MCT-15-0577-T. Epub 2016 Feb 4. PMID: 26846820; PMCID: PMC5065108. 20: Mukthavaram R, Ouyang X, Saklecha R, Jiang P, Nomura N, Pingle SC, Guo F, Makale M, Kesari S. Effect of the JAK2/STAT3 inhibitor SAR317461 on human glioblastoma tumorspheres. J Transl Med. 2015 Aug 18;13:269. doi: 10.1186/s12967-015-0627-5. PMID: 26283544; PMCID: PMC4539675.