Cevipabulin (free base)
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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.


Chemical Structure

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Cevipabulin (free base)
CAS# 849550-05-6 (free base)

Theoretical Analysis

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

Price and Availability

Size Price Availability Quantity
10.0mg USD 150.0 Same day
25.0mg USD 250.0 Same day
50.0mg USD 450.0 Same day
100.0mg USD 650.0 Same day
200.0mg USD 1150.0 Same day
500.0mg USD 1950.0 Same day
1.0g USD 3250.0 Same day
2.0g USD 4650.0 Same day
5.0g USD 7950.0 Same day
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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

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
Soluble in DMSO 16.0 34.4

Preparing Stock Solutions

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.

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. 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.

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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.



Additional Information

Related:
849550-05-6 (Cevipabulin free base)
852954-81-5 (Cevipabulin succinate, dihydrate).