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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 of CUR-61414

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

Molecular Formula C31H42N4O5
Molecular Weight 550.689
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
100.0 nM [IC50]
100.0 nM [IC50]
140.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Identification of a small molecule inhibitor of the hedgehog signaling pathway: effects on basal cell carcinoma-like lesions.
2003 Apr 15
Patents

Sample Use Guides

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
CUR6-1414 (1-5uM) blocks proliferation and induces apoptosis in basaloid lesions in mouse embryonic skin punches.
Substance Class Chemical
Created
by admin
on Sat Dec 16 02:59:48 UTC 2023
Edited
by admin
on Sat Dec 16 02:59:48 UTC 2023
Record UNII
809U4O7OQO
Record Status Validated (UNII)
Record Version
  • Download
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
Created by admin on Sat Dec 16 02:59:48 UTC 2023 , Edited by admin on Sat Dec 16 02:59:48 UTC 2023
PRIMARY
CAS
334998-36-6
Created by admin on Sat Dec 16 02:59:48 UTC 2023 , Edited by admin on Sat Dec 16 02:59:48 UTC 2023
PRIMARY
NCI_THESAURUS
C155725
Created by admin on Sat Dec 16 02:59:48 UTC 2023 , Edited by admin on Sat Dec 16 02:59:48 UTC 2023
CONCEPT
MANUFACTURER PRODUCT INFORMATION
N-((3S,5S)-1-(1,3-BENZODIOXOL-5-YLMETHYL)-5-(PIPERAZINE-1-CARBONYL)PYRROLIDIN-3-YL)-N-((3-METHOXYPHENYL)METHYL)-3,3-DIMETHYL-BUTANAMIDE
Created by admin on Sat Dec 16 02:59:48 UTC 2023 , Edited by admin on Sat Dec 16 02:59:48 UTC 2023
PRIMARY CUR61414
EPA CompTox
DTXSID00439139
Created by admin on Sat Dec 16 02:59:48 UTC 2023 , Edited by admin on Sat Dec 16 02:59:48 UTC 2023
PRIMARY
NCI_THESAURUS
C185437
Created by admin on Sat Dec 16 02:59:48 UTC 2023 , Edited by admin on Sat Dec 16 02:59:48 UTC 2023
PRIMARY
FDA UNII
809U4O7OQO
Created by admin on Sat Dec 16 02:59:48 UTC 2023 , Edited by admin on Sat Dec 16 02:59:48 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY
In mice, topical CUR61414 significantly inhibited skin Hh signaling, blocked the induction of hair follicle anagen, and shrank existing BCCs. However, we observed no clinical activity of this formulation in human superficial or nodular BCCs in a phase I clinical study.
ACTIVE MOIETY
We identified a novel small molecule Hh inhibitor (CUR61414) that can block elevated Hh signaling activity resulting from oncogenic mutations in Patched-1. Moreover, CUR61414 can suppress proliferation and induce apoptosis of basaloid nests in the BCC model systems, whereas having no effect on normal skin cells.