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 8504	100.0 nM [IC50]
Sonic hedgehog protein 1 Target ID: CHEMBL5602 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19309080	Inhibitor 8504	100.0 nM [IC50]
Smoothened homolog 20 Target ID: CHEMBL5971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22268551	Inhibitor 8504	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 438	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Targeting superficial or nodular Basal cell carcinoma with topically formulated small molecule inhibitor of smoothened.	2011-05-15	21558397
Identification of a small molecule inhibitor of the hedgehog signaling pathway: effects on basal cell carcinoma-like lesions.	2003-04-15	12679522

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

Preferred Name

English

CUR-61414

Code

English

G-024856

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