ADH-1 (brand name Exherin) is a small, cyclic pentapeptide vascular-targeting drug. It was developed by Adherex Technologies.

ADH-1
Clinical data
Trade namesExherin
ATC code
  • none
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC22H34N8O6S2
Molar mass570.68 g·mol−1
3D model (JSmol)
  • O=C(N[C@@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N)CSSC1)C(C)C)C)Cc2c[nH]cn2)C
  • InChI=1S/C22H34N8O6S2/c1-10(2)17-22(36)29-15(18(23)32)7-37-38-8-16(27-12(4)31)21(35)28-14(5-13-6-24-9-25-13)20(34)26-11(3)19(33)30-17/h6,9-11,14-17H,5,7-8H2,1-4H3,(H2,23,32)(H,24,25)(H,26,34)(H,27,31)(H,28,35)(H,29,36)(H,30,33)/t11-,14-,15-,16-,17-/m0/s1
  • Key:FQVLRGLGWNWPSS-BXBUPLCLSA-N

ADH-1 selectively and competitively binds to and blocks N-cadherin, which may result in disruption of tumor vasculature, inhibition of tumor cell growth, and the induction of tumor cell and endothelial cell apoptosis.[1] N-cadherin, a cell- surface transmembrane glycoprotein of the cadherin superfamily of proteins involved in calcium-mediated cell–cell adhesion and signaling mechanisms;[1] may be upregulated in some aggressive tumors and the endothelial cells and pericytes of some tumor blood vessels.[1]

In 2006, Adherex and NCI formed a clinical trial agreement stating that NCI will sponsor clinical trials of ADH-1 in a variety of cancer types. ADH-1 received orphan drug status from the FDA in 2008.[2]

In a pilot study (phase I trial), ADH-1 intravenous pretreatment before chemotherapy in metastatic melanoma completely destroyed tumors in half of patients. It is being investigated in phase II trials for advanced extremity melanoma.[3][4]

References

edit
  1. ^ a b c "ADH-1". NCI Drug Dictionary. 2011-02-02.
  2. ^ "ADH-1". AdisInsight. Retrieved 3 February 2017.
  3. ^ Yarom N, Stewart D, Malik R, Wells J, Avruch L, Jonker DJ (Feb 1, 2013). "Phase I clinical trial of Exherin (ADH-1) in patients with advanced solid tumors". Curr Clin Pharmacol. 8 (1): 81–88. PMID 22280327.
  4. ^ Physorg:Drug combination may be effective against deadly melanoma, pilot study shows