Exherin free base
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MedKoo CAT#: 201350

CAS#: 229971-81-7 (free base)

Description: Exherin, also known as ADH-1, is a small, cyclic pentapeptide vascular-targeting agent with potential antineoplastic and antiangiogenic activities. 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. N-cadherin, a cell- surface transmembrane glycoprotein of the cadherin superfamily of proteins involved in calcium-mediated cell-cell adhesion and signaling mechanisms; may be upregulated in some aggressive tumors and the endothelial cells and pericytes of some tumor blood vessels. Note: The old CAT# for this product was 201350A

Chemical Structure

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Exherin free base
CAS# 229971-81-7 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 201350
Name: Exherin free base
CAS#: 229971-81-7 (free base)
Chemical Formula: C22H34N8O6S2
Exact Mass: 570.20
Molecular Weight: 570.680
Elemental Analysis: C, 46.30; H, 6.01; N, 19.63; O, 16.82; S, 11.24

Price and Availability

Size Price Availability Quantity
5mg USD 90 Ready to ship
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1150 Ready to ship
500mg USD 2150 Ready to ship
1g USD 3250 Ready to ship
2g USD 5650 Ready to ship
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Related CAS #: 1135237-88-5 (TFA)   229971-81-7 (free base)  

Synonym: NSC729477; ADH1; ADH-1; ADH 1. Brand name: Exherin; Exherin free base

IUPAC/Chemical Name: (4R,7S,10S,13S,16R)-13-((1H-imidazol-5-yl)methyl)-16-acetamido-7-isopropyl-10-methyl-6,9,12,15-tetraoxo-1,2-dithia-5,8,11,14-tetraazacycloheptadecane-4-carboxamide

InChi Key: FQVLRGLGWNWPSS-BXBUPLCLSA-N

InChi Code: 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

SMILES Code: O=C([C@@H](NC([C@H](C(C)C)NC([C@H](C)NC([C@H](CC1=CN=CN1)N2)=O)=O)=O)CSSC[C@H](NC(C)=O)C2=O)N

Appearance: white 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 5% HCl aqueous solution, slightly soluble in water at room temperature, not soluble in water at low temperature.

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in 5% HCl solution or 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:    Note: The old CAT# for this product was 201350A    

Biological target: ADH-1, an N-cadherin antagonist, inhibits N-cadherin mediated cell adhesion.
In vitro activity: The number of viable cells in culture was measured using the CellTiter-Glo luminescent Cell Viability assay (Promega) at 12 h, 24 h and 48 h after addition of ADH-1 (0.25 mg/ml; 0.50 mg/ml and 1 mg/ml). ADH-1 proved to be a potent inducer of cell death in NB cell lines when added at 1 mg/ml. At this concentration, more than 50% of NB cells underwent cell death 24 h after addition (Fig. 5). Interestingly, no effect was seen on the survival of fibroblasts and N-cadherin negative epithelial cells (Fig. 5). These observations were confirmed by flow cytometric determination of PI and FITC-Annexin V levels (Figure S3). Reference: PLoS One. 2012; 7(2): e31206. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280274/
In vivo activity: ADH-1 significantly prevented tumor growth in vivo (Fig. 4b). In agreement with the IVIS data, control mice had significantly larger tumors than mice treated with ADH-1 (Fig. 4c). Control mice had significant invasion of tumor nodules into the peritoneal cavity, while tumors in mice treated with ADH-1 were small and were restricted to the pancreas. Figure 5a shows H&E staining of the stomach and a disseminated nodule of a typical control mouse (Fig. 5a, panel a). The tumor occupied the space under the villi of the stomach, indicating that N-cadherin overexpressing BxPC-3 cells were invasive. Figure 5a, panel c shows a tumor localized in the pancreas of a typical mouse treated with ADH-1. Furthermore, H&E staining showed that micro-metastases were present in 4 out of 8 the lungs of control mice (Fig. 5a, panel b), whereas no metastases were seen in mice treated with ADH-1. These data suggest that ADH-1 prevented tumor cell invasion and metastasis in an orthotopic model for pancreatic cancer using N-cadherin overexpressing BxPC-3 cells. Reference: Int J Cancer. 2008 Jan 1;122(1):71-7. https://pubmed.ncbi.nlm.nih.gov/17721921/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 2.2 3.86

Preparing Stock Solutions

The following data is based on the product molecular weight 570.68 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. Lammens T, Swerts K, Derycke L, De Craemer A, De Brouwer S, De Preter K, Van Roy N, Vandesompele J, Speleman F, Philippé J, Benoit Y, Beiske K, Bracke M, Laureys G. N-cadherin in neuroblastoma disease: expression and clinical significance. PLoS One. 2012;7(2):e31206. doi: 10.1371/journal.pone.0031206. Epub 2012 Feb 15. PMID: 22355346; PMCID: PMC3280274. 2. Shintani Y, Fukumoto Y, Chaika N, Grandgenett PM, Hollingsworth MA, Wheelock MJ, Johnson KR. ADH-1 suppresses N-cadherin-dependent pancreatic cancer progression. Int J Cancer. 2008 Jan 1;122(1):71-7. doi: 10.1002/ijc.23027. PMID: 17721921. 3. Li H, Price DK, Figg WD. ADH1, an N-cadherin inhibitor, evaluated in preclinical models of angiogenesis and androgen-independent prostate cancer. Anticancer Drugs. 2007 Jun;18(5):563-8. doi: 10.1097/CAD.0b013e328020043e. PMID: 17414625.
In vitro protocol: 1. Lammens T, Swerts K, Derycke L, De Craemer A, De Brouwer S, De Preter K, Van Roy N, Vandesompele J, Speleman F, Philippé J, Benoit Y, Beiske K, Bracke M, Laureys G. N-cadherin in neuroblastoma disease: expression and clinical significance. PLoS One. 2012;7(2):e31206. doi: 10.1371/journal.pone.0031206. Epub 2012 Feb 15. PMID: 22355346; PMCID: PMC3280274. 2. Shintani Y, Fukumoto Y, Chaika N, Grandgenett PM, Hollingsworth MA, Wheelock MJ, Johnson KR. ADH-1 suppresses N-cadherin-dependent pancreatic cancer progression. Int J Cancer. 2008 Jan 1;122(1):71-7. doi: 10.1002/ijc.23027. PMID: 17721921.
In vivo protocol: 1. Shintani Y, Fukumoto Y, Chaika N, Grandgenett PM, Hollingsworth MA, Wheelock MJ, Johnson KR. ADH-1 suppresses N-cadherin-dependent pancreatic cancer progression. Int J Cancer. 2008 Jan 1;122(1):71-7. doi: 10.1002/ijc.23027. PMID: 17721921. 2. Li H, Price DK, Figg WD. ADH1, an N-cadherin inhibitor, evaluated in preclinical models of angiogenesis and androgen-independent prostate cancer. Anticancer Drugs. 2007 Jun;18(5):563-8. doi: 10.1097/CAD.0b013e328020043e. PMID: 17414625.

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1: Leitsch D, Williams CF, Lloyd D, Duchêne M. Unexpected properties of NADP-dependent secondary alcohol dehydrogenase (ADH-1) in Trichomonas vaginalis and other microaerophilic parasites. Exp Parasitol. 2013 Jul;134(3):374-80. doi: 10.1016/j.exppara.2013.03.034. Epub 2013 Apr 8. PubMed PMID: 23578856; PubMed Central PMCID: PMC3682184.

2: Yarom N, Stewart D, Malik R, Wells J, Avruch L, Jonker DJ. Phase I clinical trial of Exherin (ADH-1) in patients with advanced solid tumors. Curr Clin Pharmacol. 2013 Feb 1;8(1):81-8. PubMed PMID: 22280327.

3: Haseba T, Kameyama K, Mashimo K, Ohno Y. Dose-Dependent Change in Elimination Kinetics of Ethanol due to Shift of Dominant Metabolizing Enzyme from ADH 1 (Class I) to ADH 3 (Class III) in Mouse. Int J Hepatol. 2012;2012:408190. doi: 10.1155/2012/408190. Epub 2011 Nov 22. PubMed PMID: 22164338; PubMed Central PMCID: PMC3227458.

4: Yarom N, Stewart D, Avruch L, Malik R, Wells J, Jonker DJ. ADH-1 in the treatment of metastatic adrenocortical carcinoma--case report. Anticancer Res. 2011 Nov;31(11):3921-5. PubMed PMID: 22110220.

5: Beasley GM, Riboh JC, Augustine CK, Zager JS, Hochwald SN, Grobmyer SR, Peterson B, Royal R, Ross MI, Tyler DS. Prospective multicenter phase II trial of systemic ADH-1 in combination with melphalan via isolated limb infusion in patients with advanced extremity melanoma. J Clin Oncol. 2011 Mar 20;29(9):1210-5. doi: 10.1200/JCO.2010.32.1224. Epub 2011 Feb 22. PubMed PMID: 21343562.

6: Beasley GM, McMahon N, Sanders G, Augustine CK, Selim MA, Peterson B, Norris R, Peters WP, Ross MI, Tyler DS. A phase 1 study of systemic ADH-1 in combination with melphalan via isolated limb infusion in patients with locally advanced in-transit malignant melanoma. Cancer. 2009 Oct 15;115(20):4766-74. doi: 10.1002/cncr.24509. PubMed PMID: 19637344.

7: Perotti A, Sessa C, Mancuso A, Noberasco C, Cresta S, Locatelli A, Carcangiu ML, Passera K, Braghetti A, Scaramuzza D, Zanaboni F, Fasolo A, Capri G, Miani M, Peters WP, Gianni L. Clinical and pharmacological phase I evaluation of Exherin (ADH-1), a selective anti-N-cadherin peptide in patients with N-cadherin-expressing solid tumours. Ann Oncol. 2009 Apr;20(4):741-5. doi: 10.1093/annonc/mdn695. Epub 2009 Feb 3. PubMed PMID: 19190075.

8: Shintani Y, Fukumoto Y, Chaika N, Grandgenett PM, Hollingsworth MA, Wheelock MJ, Johnson KR. ADH-1 suppresses N-cadherin-dependent pancreatic cancer progression. Int J Cancer. 2008 Jan 1;122(1):71-7. PubMed PMID: 17721921.

9: Kelland L. Drug evaluation: ADH-1, an N-cadherin antagonist targeting cancer vascularization. Curr Opin Mol Ther. 2007 Feb;9(1):86-91. PubMed PMID: 17330406.

10: Gomulski LM, Brogna S, Babaratsas A, Gasperi G, Zacharopoulou A, Savakis C, Bourtzis K. Molecular basis of the size polymorphism of the first intron of the Adh-1 gene of the mediterranean fruit fly, Ceratitis capitata. J Mol Evol. 2004 Jun;58(6):732-42. PubMed PMID: 15461430.

Takehara T, Teramura T, Onodera Y, Frampton J, Fukuda K. Cdh2 stabilizes FGFR1 and contributes to primed-state pluripotency in mouse epiblast stem cells. Sci Rep. 2015 Sep 30;5:14722. doi: 10.1038/srep14722. PMID: 26420260; PMCID: PMC4588589.