ADH-1

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H34N8O6S2
Molecular Weight	570.685
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]1(CSSC[C@]([H])(NC(C)=O)C(=O)N[C@@H](CC2=CNC=N2)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N1)C(N)=O

InChI

InChIKey=FQVLRGLGWNWPSS-BXBUPLCLSA-N

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

HIDE SMILES / InChI

Molecular Formula	C22H34N8O6S2
Molecular Weight	570.685
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22280327
Curator's Comment: The description was created based on several sources, including https://www.drugbank.ca/drugs/DB05485 | https://www.ncbi.nlm.nih.gov/pubmed/19637344 | https://www.ncbi.nlm.nih.gov/pubmed/22110220 | https://clinicaltrials.gov/ct2/show/NCT01825603 | https://clinicaltrials.gov/ct2/show/NCT00265057

Exherin 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. In murine melanoma xenografts, ADH-1 in combination with melphalan significantly reduced tumor growth up to 30-fold over melphalan alone. ADH-1 enhancement of response to melphalan was associated with increased formation of DNA adducts, increased apoptosis, and intracellular signaling changes. In a pilot study (phase I trial), ADH-1 intravenous pretreatment before chemotherapy in metastatic melanoma completely destroyed tumors in half of patients

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cadherin-2 2 Target ID: P19022 Gene ID: 1000.0 Gene Symbol: CDH2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17721921	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Malignant melanoma 22 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19637344	Primary	Phase I 428	Unknown Approved Use Unknown
Cancer 592 Sources: https://clinicaltrials.gov/ct2/show/NCT00264433	Primary	Phase II 1132	Unknown Approved Use Unknown
Adrenocortical carcinoma 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22110220	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
60.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19190075	600 mg/m² 3 times / 4 weeks multiple, intravenous dose: 600 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ADH-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
141.5 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19190075	1200 mg/m² 3 times / 4 weeks multiple, intravenous dose: 1200 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ADH-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
225 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19190075	2400 mg/m² 3 times / 4 weeks multiple, intravenous dose: 2400 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ADH-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
40.9 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19190075	300 mg/m² 3 times / 4 weeks multiple, intravenous dose: 300 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ADH-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
102.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19190075	600 mg/m² 3 times / 4 weeks multiple, intravenous dose: 600 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ADH-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
167.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19190075	1200 mg/m² 3 times / 4 weeks multiple, intravenous dose: 1200 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ADH-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
398.8 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19190075	2400 mg/m² 3 times / 4 weeks multiple, intravenous dose: 2400 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ADH-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
58.8 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19190075	300 mg/m² 3 times / 4 weeks multiple, intravenous dose: 300 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ADH-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
2.16 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19190075	600 mg/m² 3 times / 4 weeks multiple, intravenous dose: 600 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ADH-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.35 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19190075	1200 mg/m² 3 times / 4 weeks multiple, intravenous dose: 1200 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ADH-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.92 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19190075	2400 mg/m² 3 times / 4 weeks multiple, intravenous dose: 2400 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ADH-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19190075	300 mg/m² 3 times / 4 weeks multiple, intravenous dose: 300 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	ADH-1 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P008U2N	https://www.1pchem.com/search?query=1P008U2N
1PlusChem LLC	1P00BFMM	https://www.1pchem.com/search?query=1P00BFMM
BLD Pharm	BD629925	http://www.bldpharm.com/search/Search.html?keyword=BD629925
BLD Pharm	BD630574	http://www.bldpharm.com/search/Search.html?keyword=BD630574
Chem Scene	CS-3450	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3450
Chem Scene	CS-3607	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3607
MedChem Express	HY-13541	https://www.medchemexpress.com/search.html?q=HY-13541A&ft=&fa=&fp=
MedChem Express	HY-13541A	https://www.medchemexpress.com/search.html?q=HY-13541A&ft=&fa=&fp=
MolPort	MolPort-042-676-174	https://www.molport.com/shop/molecule-link/MolPort-042-676-174
MolPort	MolPort-046-033-511	https://www.molport.com/shop/molecule-link/MolPort-046-033-511
Molnova	M13640	https://www.molnova.com/en/serch-list.html?keywords=M13640
MuseChem	I002753	https://www.musechem.com/product/I002753.html
MuseChem	I006750	https://www.musechem.com/product/I006750.html
Ryan Scientific	LED209	https://ryansci.com/products?q=LED209&list_q=&search_type=exact
eMolecules	106277002	https://orderbb.emolecules.com/search/#?query=106277002
eMolecules	50284399	https://orderbb.emolecules.com/search/#?query=50284399
eMolecules	50550831	https://orderbb.emolecules.com/search/#?query=50550831
eMolecules	95704677	https://orderbb.emolecules.com/search/#?query=95704677
mcule	MCULE-3222806979	https://mcule.com/MCULE-3222806979/
mcule	MCULE-4596576180	https://mcule.com/MCULE-4596576180/
mcule	MCULE-4948716848	https://mcule.com/MCULE-4948716848/
mcule	MCULE-7980596038	https://mcule.com/MCULE-7980596038/

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

1000, 2000, and 4000 mg of ADH-1 administered intravenously on Days 1 and 8

Route of Administration: Intravenous

In Vitro Use Guide

Wild type, N-cadherin knockdown, or N-cadherin over-expressing BxPC-3 cells were plated for 4 hr on Transwell filters coated on both the upper and lower sides with collagen I. ADH-11 (as a control, con) or ADH-1 was added to both the upper and lower chambers (0.2 mg/ml). The number of cells/field that crossed the filter was plotted. ADH-1 significantly prevented cell migration on collagen I-coated filters in N-cadherin over-expressing cells

Substance Class	Chemical Created by `admin` on `Sat Dec 16 03:18:32 GMT 2023` Edited by `admin` on `Sat Dec 16 03:18:32 GMT 2023`
Record UNII	B058ME29VU
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ADH-1

Common Name

English

CYS-HIS-ALA-VAL-CYS

Common Name

English

NSC-729477

Code

English

L-CYSTEINAMIDE, N-ACETYL-L-CYSTEINYL-L-HISTIDYL-L-ALANYL-L-VALYL-, CYCLIC (1-5)-DISULFIDE

Common Name

English

EXHERIN

Brand Name

English

ADH 1

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1971