Zotiraciclib HCl

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MedKoo CAT#: 585245

CAS#: 1354567-82-0 (HCl)

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 HCl
CAS# 1354567-82-0 (HCl)
Instruction

Theoretical Analysis

MedKoo Cat#: 585245
Name: Zotiraciclib HCl
CAS#: 1354567-82-0 (HCl)
Chemical Formula: C23H26Cl2N4O
Exact Mass: 372.20
Molecular Weight: 445.388
Elemental Analysis: C, 62.03; H, 5.88; Cl, 15.92; N, 12.58; O, 3.59

Price and Availability

This product is not in stock, which may be available by custom synthesis. For cost-effective reason, minimum order is 1g (price is usually high, lead time is 2~3 months, depending on the technical challenge). Quote less than 1g will not be provided. To request quote, please email to sales @medkoo.com or click below button.
Note: Price will be listed if it is available in the future.

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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 HCl; Zotiraciclib hydrochloride; Zotiraciclib dihydrochloride;

IUPAC/Chemical Name: (16E)-14-methyl-20-oxa-5,7,14,27-tetrazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2(27),3,5,8,10,12(26),16,21,23-decaene dihydrochloride

InChi Key: QKXVFRYVDFOHSF-WTVBWJGASA-N

InChi Code: InChI=1S/C23H24N4O.2ClH/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);2*1H/b3-2+;;

SMILES Code: CN(CC1=CC2=CC=C1)C/C=C/CCOC3=CC=CC(C4=NC(N2)=NC=C4)=C3.[H]Cl.[H]Cl

Appearance: 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

Shelf Life: >3 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:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 445.39 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:
In vivo protocol:

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1: Su YT, Chen R, Wang H, Song H, Zhang Q, Chen LY, Lappin H, Vasconcelos G, Lita A, Maric D, Li A, Celiku O, Zhang W, Meetze K, Estok T, Larion M, Abu-Asab M, Zhuang Z, Yang C, Gilbert MR, Wu J. Novel Targeting of Transcription and Metabolism in Glioblastoma. Clin Cancer Res. 2018 Mar 1;24(5):1124-1137. doi: 10.1158/1078-0432.CCR-17-2032. Epub 2017 Dec 18. PubMed PMID: 29254993.

2: Ponder KG, Matulis SM, Hitosugi S, Gupta VA, Sharp C, Burrows F, Nooka AK, Kaufman JL, Lonial S, Boise LH. Dual inhibition of Mcl-1 by the combination of carfilzomib and TG02 in multiple myeloma. Cancer Biol Ther. 2016 Jul 2;17(7):769-77. doi: 10.1080/15384047.2016.1192086. PubMed PMID: 27246906; PubMed Central PMCID: PMC4970534.

3: Shah SP, Nooka AK, Lonial S, Boise LH. TG02 inhibits proteasome inhibitor-induced HSF1 serine 326 phosphorylation and heat shock response in multiple myeloma. Blood Adv. 2017 Sep 26;1(21):1848-1853. doi: 10.1182/bloodadvances.2017006122. eCollection 2017 Sep 26. PubMed PMID: 29296831; PubMed Central PMCID: PMC5728095.

4: 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.

5: Li K, Zhou X, Wang W, Gao Y, Zhao G, Tao E, Xu K. Centimeter-Level Orbit Determination for TG02 Spacelab Using Onboard GNSS Data. Sensors (Basel). 2018 Aug 14;18(8). pii: E2671. doi: 10.3390/s18082671. PubMed PMID: 30110935; PubMed Central PMCID: PMC6111924.

6: Pallis M, Burrows F, Ryan J, Grundy M, Seedhouse C, Abdul-Aziz A, Montero J, Letai A, Russell N. Complementary dynamic BH3 profiles predict co-operativity between the multi-kinase inhibitor TG02 and the BH3 mimetic ABT-199 in acute myeloid leukaemia cells. Oncotarget. 2017 Mar 7;8(10):16220-16232. doi: 10.18632/oncotarget.8742. PubMed PMID: 27092880; PubMed Central PMCID: PMC5369958.

7: 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.

8: Le Rhun E, von Achenbach C, Lohmann B, Silginer M, Schneider H, Meetze K, Szabo E, Weller M. Profound, durable and MGMT-independent sensitivity of glioblastoma cells to cyclin-dependent kinase inhibition. Int J Cancer. 2019 Jul 1;145(1):242-253. doi: 10.1002/ijc.32069. Epub 2019 Jan 12. PubMed PMID: 30549269.

9: 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.

10: Álvarez-Fernández S, Ortiz-Ruiz MJ, Parrott T, Zaknoen S, Ocio EM, San Miguel J, Burrows FJ, Esparís-Ogando A, Pandiella A. Potent antimyeloma activity of a novel ERK5/CDK inhibitor. Clin Cancer Res. 2013 May 15;19(10):2677-87. doi: 10.1158/1078-0432.CCR-12-2118. Epub 2013 Mar 26. PubMed PMID: 23532886.

11: 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.

12: 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.

13: Lyle L, Daver N. Current and emerging therapies for patients with acute myeloid leukemia: a focus on MCL-1 and the CDK9 pathway. Am J Manag Care. 2018 Aug;24(16 Suppl):S356-S365. PubMed PMID: 30132679.

14: Aleem E, Arceci RJ. Targeting cell cycle regulators in hematologic malignancies. Front Cell Dev Biol. 2015 Apr 9;3:16. doi: 10.3389/fcell.2015.00016. eCollection 2015. Review. PubMed PMID: 25914884; PubMed Central PMCID: PMC4390903.

15: Ortiz-Ruiz MJ, Álvarez-Fernández S, Parrott T, Zaknoen S, Burrows FJ, Ocaña A, Pandiella A, Esparís-Ogando A. Therapeutic potential of ERK5 targeting in triple negative breast cancer. Oncotarget. 2014 Nov 30;5(22):11308-18. PubMed PMID: 25350956; PubMed Central PMCID: PMC4294347.

16: Blachly JS, Byrd JC, Grever M. Cyclin-dependent kinase inhibitors for the treatment of chronic lymphocytic leukemia. Semin Oncol. 2016 Apr;43(2):265-73. doi: 10.1053/j.seminoncol.2016.02.003. Epub 2016 Feb 8. Review. PubMed PMID: 27040705.

17: Guglielmone AA, Volpogni MM, Quaino OR, Anziani OS, Mangold AJ. Abundance of stable flies on heifers treated for control of horn flies with organophosphate impregnated ear tags. Med Vet Entomol. 2004 Mar;18(1):10-3. PubMed PMID: 15009440.

18: William AD, Lee AC. Acid Mediated Ring Closing Metathesis: A Powerful Synthetic Tool Enabling the Synthesis of Clinical Stage Kinase Inhibitors. Chimia (Aarau). 2015;69(3):142-5. doi: 10.2533/chimia.2015.142. PubMed PMID: 26507218.

19: Pallis M, Burrows F, Whittall A, Boddy N, Seedhouse C, Russell N. Efficacy of RNA polymerase II inhibitors in targeting dormant leukaemia cells. BMC Pharmacol Toxicol. 2013 Jun 15;14:32. doi: 10.1186/2050-6511-14-32. PubMed PMID: 23767415; PubMed Central PMCID: PMC3685571.

20: Patra D, Chaaban AH, Darwish S, Saad HA, Nehme AS, Ghaddar TH. Time resolved study of three ruthenium(II) complexes at micellar surfaces: A new long excited state lifetime probe for determining critical micelle concentration of surfactant nano-aggregates. Colloids Surf B Biointerfaces. 2016 Feb 1;138:32-40. doi: 10.1016/j.colsurfb.2015.11.037. Epub 2015 Nov 23. PubMed PMID: 26642074.