WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200730
CAS#: 849550-05-6 (free base)
Description: Cevipabulin (free base), also known as TTI-237, an antimicrotubule agent, is a small synthetic molecule of triazolopyrimidine derivative with potential antitumor activity. With a novel mechanism of action distinct from the action of other vinca alkaloid compounds, TTI-237 specifically binds to tubulin at the vinca site, and promotes the polymerization of tubulin into microtubules. TTI-237 stabilizes tubulin and inhibits microtubule disassembly. This results in cell cycle arrest at the G2/M phase, and leading to cell death.
MedKoo Cat#: 200730
Name: Cevipabulin (free base)
CAS#: 849550-05-6 (free base)
Chemical Formula: C18H18ClF5N6O
Exact Mass: 464.11508
Molecular Weight: 464.82
Elemental Analysis: C, 46.51; H, 3.90; Cl, 7.63; F, 20.44; N, 18.08; O, 3.44
Related CAS #: 849550-05-6 (free base) 852954-81-5 (succinate) 849550-69-2 (fumarate)
Synonym: TTI 237; TTI-237; TTI237; D06576; D 06576; D-06576; Cevipabulin.
IUPAC/Chemical Name: 5-chloro-6-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-N-[(1S)-2,2,2-trifluoro-1- methylethyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine.
InChi Key: ZUZPCOQWSYNWLU-VIFPVBQESA-N
InChi Code: InChI=1S/C18H18ClF5N6O/c1-9(18(22,23)24)28-16-14(15(19)29-17-26-8-27-30(16)17)13-11(20)6-10(7-12(13)21)31-5-3-4-25-2/h6-9,25,28H,3-5H2,1-2H3/t9-/m0/s1
SMILES Code: C[C@H](NC1=C(C2=C(F)C=C(OCCCNC)C=C2F)C(Cl)=NC3=NC=NN13)C(F)(F)F
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, 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: | Cevipabulin (TTI-237) is a, microtubule-active antitumor compound and inhibits the binding of [3H] vinblastine to tubulin, with an IC50 of 18-40 nM for cytotoxicity in human tumor cell line. |
| In vitro activity: | To elucidate the cellular effect of cevipabulin at an early time point, a label-free quantitative proteomic analysis was carried out on a 6-hour cevipabulin-treated human cervical adenocarcinoma cell line HeLa. Cevipabulin significantly down-regulated the protein level of α-tubulin, β-tubulin, and their isoforms with high selectivity (Fig. 1A). Immunoblotting study confirmed that cevipabulin decreased tubulin proteins in HeLa, human colon colorectal carcinoma cell line Hct116, human large cell lung carcinoma cell line H460, and human B cell lymphoma cell SU-DHL-6 in a dose-dependent (Fig. 1B) and time-dependent manner in HeLa cells (Fig. 1C), demonstrating that the reduction of tubulin was a common biochemical consequence of cevipabulin treatment in cancer cells. The quantitative PCR assay showed that cevipabulin had no effect on α- and β-tubulin mRNA levels (Fig. 1D), indicating that the downregulation of tubulin protein treated by cevipabulin was posttranscriptional. N-carbobenzyloxy-L-leucyl-L-leucyl-L-leucinal (MG132), a proteasome inhibitor, could completely block cevipabulin-induced tubulin degradation (Fig. 1E). All these proved that cevipabulin promotes tubulin degradation in a proteasome-dependent pathway. Reference: Sci Adv. 2021 May 19;7(21):eabg4168. https://advances.sciencemag.org/content/7/21/eabg4168 |
| In vivo activity: | TTI-237 was tested for antitumor efficacy in two mouse xenograft models. In the first, the compound, which has excellent solubility in water, was formulated in 0.9% saline and given i.v. to athymic mice bearing staged tumors of LoVo human colon adenocarcinoma. The compound was given every 4 days for four cycles at doses of 5, 10, 15, and 20 mg/kg/dose. The compound showed dosedependent effects, with good antitumor activity at 20 and 15 mg/kg ( Fig. 6A ). In the second model, U87-MG human glioblastoma, TTI-237 was given both i.v. and p.o. at a single dose of 25 mg/kg to tumor-bearing mice. The compound was about equally effective by the two routes ( Fig. 6B). Reference: Cancer Res. 2008 Apr 1;68(7):2292-300. https://cancerres.aacrjournals.org/content/68/7/2292.long |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| Soluble in DMSO | 16.0 | 34.4 |
The following data is based on the product molecular weight 464.82 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 |
| Formulation protocol: | 1. Yang J, Yu Y, Li Y, Yan W, Ye H, Niu L, Tang M, Wang Z, Yang Z, Pei H, Wei H, Zhao M, Wen J, Yang L, Ouyang L, Wei Y, Chen Q, Li W, Chen L. Cevipabulin-tubulin complex reveals a novel agent binding site on α-tubulin with tubulin degradation effect. Sci Adv. 2021 May 19;7(21):eabg4168. doi: 10.1126/sciadv.abg4168. PMID: 34138737; PMCID: PMC8133757. 2. Beyer CF, Zhang N, Hernandez R, Vitale D, Lucas J, Nguyen T, Discafani C, Ayral-Kaloustian S, Gibbons JJ. TTI-237: a novel microtubule-active compound with in vivo antitumor activity. Cancer Res. 2008 Apr 1;68(7):2292-300. doi: 10.1158/00085472.CAN-07-1420. PMID: 18381436 |
| In vitro protocol: | 1. Yang J, Yu Y, Li Y, Yan W, Ye H, Niu L, Tang M, Wang Z, Yang Z, Pei H, Wei H, Zhao M, Wen J, Yang L, Ouyang L, Wei Y, Chen Q, Li W, Chen L. Cevipabulin-tubulin complex reveals a novel agent binding site on α-tubulin with tubulin degradation effect. Sci Adv. 2021 May 19;7(21):eabg4168. doi: 10.1126/sciadv.abg4168. PMID: 34138737; PMCID: PMC8133757. 2. Beyer CF, Zhang N, Hernandez R, Vitale D, Lucas J, Nguyen T, Discafani C, Ayral-Kaloustian S, Gibbons JJ. TTI-237: a novel microtubule-active compound with in vivo antitumor activity. Cancer Res. 2008 Apr 1;68(7):2292-300. doi: 10.1158/00085472.CAN-07-1420. PMID: 18381436 |
| In vivo protocol: | 1. Beyer CF, Zhang N, Hernandez R, Vitale D, Lucas J, Nguyen T, Discafani C, Ayral-Kaloustian S, Gibbons JJ. TTI-237: a novel microtubule-active compound with in vivo antitumor activity. Cancer Res. 2008 Apr 1;68(7):2292-300. doi: 10.1158/00085472.CAN-07-1420. PMID: 18381436. |
1: Wang-Gillam A, Arnold SM, Bukowski RM, Rothenberg ML, Cooper W, Wang KK, Gauthier E, Lockhart AC. A phase I dose escalation study of TTI-237 in patients with advanced malignant solid tumors. Invest New Drugs. 2012 Feb;30(1):266-72. Epub 2010 Aug 10. PubMed PMID: 20697774.
2: Ayral-Kaloustian S, Zhang N, Beyer C. Cevipabulin (TTI-237): preclinical and clinical results for a novel antimicrotubule agent. Methods Find Exp Clin Pharmacol. 2009 Sep;31(7):443-7. Review. PubMed PMID: 19907719.
3: Beyer CF, Zhang N, Hernandez R, Vitale D, Nguyen T, Ayral-Kaloustian S, Gibbons JJ. The microtubule-active antitumor compound TTI-237 has both paclitaxel-like and vincristine-like properties. Cancer Chemother Pharmacol. 2009 Sep;64(4):681-9. Epub 2009 Jan 10. PubMed PMID: 19132373.
4: Beyer CF, Zhang N, Hernandez R, Vitale D, Lucas J, Nguyen T, Discafani C, Ayral-Kaloustian S, Gibbons JJ. TTI-237: a novel microtubule-active compound with in vivo antitumor activity. Cancer Res. 2008 Apr 1;68(7):2292-300. PubMed PMID: 18381436.
5: Zhang N, Ayral-Kaloustian S, Nguyen T, Hernandez R, Beyer C. 2-cyanoaminopyrimidines as a class of antitumor agents that promote tubulin polymerization. Bioorg Med Chem Lett. 2007 Jun 1;17(11):3003-5. Epub 2007 Mar 25. PubMed PMID: 17416524.
Related:
849550-05-6 (Cevipabulin free base)
852954-81-5 (Cevipabulin succinate, dihydrate).
