CUR-61414

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C31H42N4O5
Molecular Weight	550.689
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=CC(CN([C@H]2C[C@H](N(CC3=CC4=C(OCO4)C=C3)C2)C(=O)N5CCNCC5)C(=O)CC(C)(C)C)=C1

InChI

InChIKey=WPHXYKUPFJRJDK-AHWVRZQESA-N

InChI=1S/C31H42N4O5/c1-31(2,3)17-29(36)35(19-22-6-5-7-25(14-22)38-4)24-16-26(30(37)33-12-10-32-11-13-33)34(20-24)18-23-8-9-27-28(15-23)40-21-39-27/h5-9,14-15,24,26,32H,10-13,16-21H2,1-4H3/t24-,26-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12679522 | https://www.ncbi.nlm.nih.gov/pubmed/14747845
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/24550577 | https://www.ncbi.nlm.nih.gov/pubmed/21558397

CUR-61414 is a novel small molecule Hh inhibitor that can block elevated Hh signaling activity resulting from oncogenic mutations in Patched-1. CUR-61414 can suppress proliferation and induce apoptosis of basaloid nests in the BCC model systems, whereas having no effect on normal skin cells. Cur-61414 was successful in eradicating the basal cell carcinomas in mouse ex-vivo model but failed in phase I trials in humans as it could not penetrate the human skin.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Hedgehog signaling pathway 11 Target ID: map04340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12679522	Inhibitor 8297	100.0 nM [IC50]
Sonic hedgehog protein 1 Target ID: CHEMBL5602 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19309080	Inhibitor 8297	100.0 nM [IC50]
Smoothened homolog 20 Target ID: CHEMBL5971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22268551	Inhibitor 8297	140.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Basal cell carcinoma 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14747845 https://www.ncbi.nlm.nih.gov/pubmed/19309080	Primary		Phase I 428	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Identification of a small molecule inhibitor of the hedgehog signaling pathway: effects on basal cell carcinoma-like lesions.	2003 Apr 15	12679522
Targeting superficial or nodular Basal cell carcinoma with topically formulated small molecule inhibitor of smoothened.	2011 May 15	21558397

Patents

Sample Use Guides

In Vivo Use Guide

To determine whether CUR-61414 can block Hh pathway activation in mouse depilatory model, two doses of cream were applied containing 1–3% CUR-61414. Two percent CUR-61414 caused maximal repression of Gli1 expression. Application of 2% CUR-61414 twice daily over 3 days was more effective than once daily application (7-fold vs 3-fold Gli1 down-regulation).

Route of Administration: Topical

In Vitro Use Guide

CUR6-1414 (1-5uM) blocks proliferation and induces apoptosis in basaloid lesions in mouse embryonic skin punches.

Name

Type

Language

CUR-61414

Code

English

G-024856

Code

English

CUR 61414

Code

English

BUTANAMIDE, N-((3S,5S)-1-(1,3-BENZODIOXOL-5-YLMETHYL)-5-(1-PIPERAZINYLCARBONYL)-3-PYRROLIDINYL)-N-((3-METHOXYPHENYL)METHYL)-3,3-DIMETHYL-

Systematic Name

English

N-((3S,5S)-1-(1,3-BENZODIOXOL-5-YLMETHYL)-5-(PIPERAZINE-1-CARBONYL)PYRROLIDIN-3-YL)-N-((3-METHOXYPHENYL)METHYL)-3,3-DIMETHYL-BUTANAMIDE

Systematic Name

English

N-((3S,5S)-1-(1,3-BENZODIOXOL-5-YLMETHYL)-5-(1-PIPERAZINYLCARBONYL)-3-PYRROLIDINYL)-N-((3-METHOXYPHENYL)METHYL)-3,3-DIMETHYLBUTANAMIDE

Systematic Name

English

Code System Code Type Description

PUBCHEM

10392802