Cevipabulin (free base)| TTI-237 | CAS#849550-05-6 (free base) | antimicrotubule agent

MedKoo Cat#: 200730 | Name: Cevipabulin (free base)

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

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: 464.1151

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
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 325.00	Ready to ship
50mg	USD 550.00	Ready to ship
100mg	USD 950.00	Ready to ship
200mg	USD 1,650.00	Ready to ship
500mg	USD 3,450.00	Ready to ship

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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

More Info

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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#BBC41030

QC Data

View QC data: current batch, Lot#BBC41030

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	Soluble in DMSO	16.0	34.40

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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:

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: Nasrin SR, Rashedul Kabir AM, Konagaya A, Ishihara T, Sada K, Kakugo A. Stabilization of microtubules by cevipabulin. Biochem Biophys Res Commun. 2019 Aug 27;516(3):760-764. doi: 10.1016/j.bbrc.2019.06.095. Epub 2019 Jun 26. PMID: 31253401. 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. doi: 10.1358/mf.2009.31.7.1410793. PMID: 19907719. 3: 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. 4: Merugu SR, Cherukupalli S, Karpoormath R. An Overview on Synthetic and Medicinal Perspectives of [1,2,4]Triazolo[1,5-a]pyrimidine Scaffold. Chem Biodivers. 2022 Sep;19(9):e202200291. doi: 10.1002/cbdv.202200291. Epub 2022 Aug 10. PMID: 35946991. 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. doi: 10.1016/j.bmcl.2007.03.070. Epub 2007 Mar 25. PMID: 17416524. 6: Yao Y, Nzou G, Alle T, Tsering W, Maimaiti S, Trojanowski JQ, Lee VM, Ballatore C, Brunden KR. Correction of microtubule defects within Aβ plaque- associated dystrophic axons results in lowered Aβ release and plaque deposition. Alzheimers Dement. 2020 Oct;16(10):1345-1357. doi: 10.1002/alz.12144. Epub 2020 Sep 11. PMID: 32918367; PMCID: PMC7652013. 7: 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. doi: 10.1007/s00280-008-0916-2. Epub 2009 Jan 10. PMID: 19132373. 8: 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. doi: 10.1007/s10637-010-9506-3. Epub 2010 Aug 10. PMID: 20697774. 9: 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: 10.1158/0008-5472.CAN-07-1420. PMID: 18381436. 10: Kovalevich J, Cornec AS, Yao Y, James M, Crowe A, Lee VM, Trojanowski JQ, Smith AB 3rd, Ballatore C, Brunden KR. Characterization of Brain-Penetrant Pyrimidine-Containing Molecules with Differential Microtubule-Stabilizing Activities Developed as Potential Therapeutic Agents for Alzheimer's Disease and Related Tauopathies. J Pharmacol Exp Ther. 2016 May;357(2):432-50. doi: 10.1124/jpet.115.231175. Epub 2016 Mar 15. PMID: 26980057; PMCID: PMC4851320.