Zotiraciclib free base
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MedKoo CAT#: 205642

CAS#: 937270-47-8 (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.

Chemical Structure

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Zotiraciclib free base
CAS# 937270-47-8 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 205642
Name: Zotiraciclib free base
CAS#: 937270-47-8 (free base)
Chemical Formula: C23H24N4O
Exact Mass: 372.20
Molecular Weight: 372.460
Elemental Analysis: C, 74.17; H, 6.49; N, 15.04; O, 4.30

Price and Availability

Size Price Availability Quantity
10mg USD 250 Ready to ship
25mg USD 550 Ready to ship
50mg USD 950 Ready to ship
5mg USD 150 Ready to ship
100mg USD 1650 Ready to ship
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Related CAS #: 1354567-82-0 (HCl), 1204918-73-9 (citrate), 1204918-72-8 (free base), 937270-47-8 (free base),

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[19.3.1.12,6.18,12]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

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

Biological target: Zotiraciclib (TG02; SB1317) is a potent inhibitor of CDK2, JAK2, and FLT3 for the treatment of cancer, with IC50s of 13, 73, and 56 nM for CDK2, JAK2 and FLT3, respectively.
In vitro activity: Zotiraciclib (SB1317) was soluble, highly permeable in Caco-2 cells, and showed > 99% binding to plasma from mice, dog and humans. It was metabolically stable in human and dog liver microsomes relative to mouse and rat. SB1317 was mainly metabolized by CYP3A4 and CY1A2 in vitro. SB1317 did not inhibit any of the major human CYPs in vitro except CYP2D6 (IC50=1 μM). SB1317 did not significantly induce CYP1A and CYP3A4 in human hepatocytes in vitro. The metabolic profiles in liver microsomes from preclinical species were qualitatively similar to humans. Reference: Drug Metab Lett. 2012 Mar;6(1):33-42. http://www.eurekaselect.com/97785/article
In vivo activity: Two models were selected based on their relevance in cancer: HCT-116 colon cancer and Ramos B-cell lymphoma. Prior to conducting both experiments, dosing regimes in each model were explored and optimal schedules selected for each model that would be tolerated for the duration of the experiment. In the colon cancer model, HCT-116 cells were injected subcutaneously and tumors were established with mean group sizes of approximately 100 mm3. Treatment with Zotiraciclib (26h) at doses of 50 and 75 mg/kg po 3 times per week on a Monday, Wednesday, Friday schedule was started 8 days after cell inoculation for 15 days. Treatment with 26h at 75 mg/kg po q.d. 3×/week significantly inhibited the growth of tumors with a mean TGI of 82%, while the lower dose of 50 mg/kg po 3×/week was marginally effective (Figure 9). In the lymphoma model Ramos cells were injected subcutaneously and tumors were established with mean group sizes of approximately 200 mm3. Two different dosing regimens of 26h were explored in this model: 75 mg/kg po q.d. on a 2 days on and 5 days off schedule and 15 mg/kg ip q.d. on a 5 days on 5 days off schedule were started 12 days after cell inoculation for 15 days. There were two vehicle control groups that received either MC/Tween or DMA/CRE (see Experimental Section for details). The treatment groups were compared with the corresponding vehicle control groups for assessment of percentage TGI. Treatment with 26h using either regime significantly inhibited the growth of tumors with mean TGIs of 42% and 63% for the oral and ip delivery methods, respectively (Figure 10). Reference: J Med Chem. 2012 Jan 12;55(1):169-96. https://doi.org/10.1021/jm201112g

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 26.5 71.15
DMSO 26.5 71.15

Preparing Stock Solutions

The following data is based on the product molecular weight 372.460000000000000000000000000000 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:
In vitro protocol: 1. 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. doi: 10.2174/187231212800229336. PMID: 22372550.
In vivo protocol: 1. 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[19.3.1.1(2,6).1(8,12)]heptacosa-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. PMID: 22148278.

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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[19.3.1.1(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.