WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205642
CAS#: 1204918-72-8 (free base)
Description: Zotiraciclib, also known as TG02 and SB1317, is a novel small molecule potent CDK/JAK2/FLT3 inhibitor. Zotiraciclib may be useful for the treatment of cancer that crosses the blood brain barrier and acts by depleting Myc through the inhibition of cyclin-dependent kinase 9 (CDK9). It is one of a number of CDK inhibitors under investigation; others targeting CDK9 for the treatment of acute myeloid leukemia include alvocidib and atuveciclib. Myc overexpression is a known factor in many cancers, with 80 percent of glioblastomas characterized by this property.
MedKoo Cat#: 205642
Name: Zotiraciclib free base
CAS#: 1204918-72-8 (free base)
Chemical Formula: C23H24N4O
Exact Mass: 372.19501
Molecular Weight: 372.46
Elemental Analysis: C, 74.17; H, 6.49; N, 15.04; O, 4.30
Zotiraciclib free base (TG02) is in stock. The same day ship out after order is received.
Synonym: Ex45; Ex-45; EX 45; TG02; TG 02; TG02; SB1317; SB1317; SB 1317; Zotiraciclib; Zotiraciclib free base;
IUPAC/Chemical Name: 20-Oxa-5,7,14,27-tetraazatetracyclo[18.104.22.168,6.18,12]heptacosa-1(25),2,4,6(27),8,10,12(26),16,21,23-decaene, 14-methyl-
InChi Key: VXBAJLGYBMTJCY-NSCUHMNNSA-N
InChi Code: InChI=1S/C23H24N4O/c1-27-13-3-2-4-14-28-21-10-6-8-19(16-21)22-11-12-24-23(26-22)25-20-9-5-7-18(15-20)17-27/h2-3,5-12,15-16H,4,13-14,17H2,1H3,(H,24,25,26)/b3-2+
SMILES Code: CN(C/C=C/CCO1)CC2=CC(NC3=NC(C4=CC1=CC=C4)=CC=N3)=CC=C2
The following data is based on the product molecular weight 372.46 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.
|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|
1: Pallis M, Abdul-Aziz A, Burrows F, Seedhouse C, Grundy M, Russell N. The multi-kinase inhibitor TG02 overcomes signalling activation by survival factors to deplete MCL1 and XIAP and induce cell death in primary acute myeloid leukaemia cells. Br J Haematol. 2012 Oct;159(2):191-203. doi: 10.1111/bjh.12018. Epub 2012 Aug 30. PubMed PMID: 22934750.
2: Poulsen A, William A, Blanchard S, Nagaraj H, Williams M, Wang H, Lee A, Sun E, Teo EL, Tan E, Goh KC, Dymock B. Structure-based design of nitrogen-linked macrocyclic kinase inhibitors leading to the clinical candidate SB1317/TG02, a potent inhibitor of cyclin dependant kinases (CDKs), Janus kinase 2 (JAK2), and Fms-like tyrosine kinase-3 (FLT3). J Mol Model. 2013 Jan;19(1):119-30. doi: 10.1007/s00894-012-1528-7. Epub 2012 Jul 22. PubMed PMID: 22820730.
3: Pasha MK, Jayaraman R, Reddy VP, Yeo P, Goh E, Williams A, Goh KC, Kantharaj E. Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42. PubMed PMID: 22372550.
4: William AD, Lee AC, Goh KC, Blanchard S, Poulsen A, Teo EL, Nagaraj H, Lee CP, Wang H, Williams M, Sun ET, Hu C, Jayaraman R, Pasha MK, Ethirajulu K, Wood JM, Dymock BW. Discovery of kinase spectrum selective macrocycle (16E)-14-methyl-20-oxa-5,7,14,26-tetraazatetracyclo[22.214.171.124(2,6).1(8,12)]heptaco sa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (SB1317/TG02), a potent inhibitor of cyclin dependent kinases (CDKs), Janus kinase 2 (JAK2), and fms-like tyrosine kinase-3 (FLT3) for the treatment of cancer. J Med Chem. 2012 Jan 12;55(1):169-96. doi: 10.1021/jm201112g. Epub 2011 Dec 29. PubMed PMID: 22148278.
5: Goh KC, Novotny-Diermayr V, Hart S, Ong LC, Loh YK, Cheong A, Tan YC, Hu C, Jayaraman R, William AD, Sun ET, Dymock BW, Ong KH, Ethirajulu K, Burrows F, Wood JM. TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti-leukemic properties. Leukemia. 2012 Feb;26(2):236-43. doi: 10.1038/leu.2011.218. Epub 2011 Aug 23. PubMed PMID: 21860433.
TG02 was shown to be a 10-50nM inhibitor of CDKs 1,2,7 and 9 and other ongogenic kinases, including FLT3, JAK2 and ERK5. TG02 potently inhibits proliferation across a broad panel of human solid tumor cell lines (n = 15, IC50 from 64 to 504 nM). This potency exceeded that of other pan-CDK inhibitors currently in clinical development (SNS-032 and seliciclib) and other drugs that block FLT3 and JAK2 but lack CDK activity (sunitinib and TG101348), suggesting that the unique spectrum of kinases inhibited by TG02 may provide enhanced antitumor activity in solid tumors. TG02 potently induced G2/M cell cycle arrest that rapidly progressed to robust apoptosis in HCT116 cells and synergized with doxorubicin in pancreatic and breast cancer cell lines and with gemcitabine in ovarian carcinoma cells. TG02 was cleared from the blood within 8 hours of PO dosing but was retained in tumor masses at supratherapeutic levels for 24-48 h, depending on dose. Accordingly, pathway-related biomarkers were markedly suppressed for 24-72 h after dosing. In mice bearing SC HCT116 xenografts, TG02 inhibited tumor growth by 82% (p<0.001) at 75 mg/kg PO Q2D. Conclusions: TG02 is a multi-kinase inhibitor with a previously unreported spectrum of targets that shows promising preclinical activity for the treatment of solid tumors in man. (source: J Clin Oncol 28, 2010 (suppl; abstr e13549)