CKD-516

• CAT Number: I010176
• CAS Number: 1188371-47-2
• Molecular Formula: C26H28N6O5S
• Molecular Weight: 536.607
• Purity: ≥95%
• Synonyms: CKD-516
• Storage: Store at -20°C
• Related CAS: 1240321-53-2 ( HCl salt)
• IUPAC Name: (2S)-2-amino-3-methyl-N-[4-[3-(1,2,4-triazol-1-yl)-4-(3,4,5-trimethoxybenzoyl)phenyl]-1,3-thiazol-2-yl]butanamide
• InChI: InChI=1S/C26H28N6O5S/c1-14(2)22(27)25(34)31-26-30-18(11-38-26)15-6-7-17(19(8-15)32-13-28-12-29-32)23(33)16-9-20(35-3)24(37-5)21(10-16)36-4/h6-14,22H,27H2,1-5H3,(H,30,31,34)/t22-/m0/s1
• InChIKey: UKKRUIXIDCWALA-QFIPXVFZSA-N
• SMILES: CC(C)C(C(=O)NC1=NC(=CS1)C2=CC(=C(C=C2)C(=O)C3=CC(=C(C(=C3)OC)OC)OC)N4C=NC=N4)N

CKD-516 (CAT: I010176) is a valine prodrug of (S516) and functions as a vascular disrupting agent (VDA) with potential applications in the treatment of solid cancers. It acts as a tubulin inhibitor, specifically targeting the tubulin of the endothelial cytoskeleton. By selectively disrupting tubulin, CKD-516 interferes with the formation and stability of microtubules in endothelial cells, leading to the disruption of the tumor vasculature. This disruption of the tumor blood supply can result in tumor regression and inhibition of tumor growth. CKD-516’s ability to selectively target endothelial tubulin makes it a promising candidate for the treatment of solid cancers.

Overview of Clinical Research

CKD-516 was initiated phase 1 trial in Korea in 2010.  In Dec 2014, Phase-I clinical trials in Solid tumours in South Korea was on going.

Reference

1: Kim KW, Lee JM, Jeon YS, Lee IJ, Choi Y, Park J, Kiefer B, Kim C, Han JK, Choi BI. Vascular disrupting effect of CKD-516: preclinical study using DCE-MRI. Invest New Drugs. 2013 Oct;31(5):1097-106. doi: 10.1007/s10637-012-9915-6. Epub 2013 Jan 9. Erratum in: Invest New Drugs. 2013 Oct;31(5):1397. PubMed PMID: 23299389.
2: Kim YI, Kim KW, Lee HK, Park J, Chung JW, Youn H, Kim SJ, Kim DH, Tseng JC, Lee JM. Enhanced efficacy of CKD-516 in combination with doxorubicin: pre-clinical evaluation using a hepatocellular carcinoma xenograft model. Anticancer Res. 2014 Apr;34(4):1715-22. PubMed PMID: 24692701.
3: Moon CH, Lee SJ, Lee HY, Dung le TK, Cho WJ, Cha H, Park JW, Min YJ. CKD-516 displays vascular disrupting properties and enhances anti-tumor activity in combination with chemotherapy in a murine tumor model. Invest New Drugs. 2014 Jun;32(3):400-11. doi: 10.1007/s10637-013-0043-8. Epub 2013 Nov 8. PubMed PMID: 24202729.
4: Joo I, Kim JH, Lee JM, Choi JW, Han JK, Choi BI. Early quantification of the therapeutic efficacy of the vascular disrupting agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2 liver tumors. Ultrasonography. 2014 Jan;33(1):18-25. doi: 10.14366/usg.13006. Epub 2013 Nov 15. PubMed PMID: 24936491; PubMed Central PMCID: PMC4058966.
5: Joo I, Lee JM, Han JK, Choi BI. Intravoxel incoherent motion diffusion-weighted MR imaging for monitoring the therapeutic efficacy of the vascular disrupting agent CKD-516 in rabbit VX2 liver tumors. Radiology. 2014 Aug;272(2):417-26. doi: 10.1148/radiol.14131165. Epub 2014 Apr 3. PubMed PMID: 24697148.
6: Oh DY, Kim TM, Han SW, Shin DY, Lee YG, Lee KW, Kim JH, Kim TY, Jang IJ, Lee JS, Bang YJ. Phase I Study of CKD-516, a Novel Vascular Disrupting Agent, in Patients with Advanced Solid Tumors. Cancer Res Treat. 2016 Jan;48(1):28-36. doi: 10.4143/crt.2014.258. Epub 2015 Feb 23. PubMed PMID: 25715767; PubMed Central PMCID: PMC4720091.
7: Lee J, Kim SJ, Choi H, Kim YH, Lim IT, Yang HM, Lee CS, Kang HR, Ahn SK, Moon SK, Kim DH, Lee S, Choi NS, Lee KJ. Identification of CKD-516: a potent tubulin polymerization inhibitor with marked antitumor activity against murine and human solid tumors. J Med Chem. 2010 Sep 9;53(17):6337-54. doi: 10.1021/jm1002414. PubMed PMID: 20690624.