Details of the Drug

General Information of Drug (ID: DMEM2SW)

• Drug Name: CYCLOPAMINE
• Synonyms: CYCLOPAMINE; 11-Deoxojervine; 4449-51-8; UNII-ZH658AJ192; CHEMBL254129; CHEBI:4021; 11-Deoxyjervine; ZH658AJ192; HSDB 3505; Jervine, 11-deoxo-; Spiro[9H-benzo[a]fluorene-9,2'(3'H)-furo[3,2-b]pyridin]-3-ol, 1,2,3,3'a,4,4',5',6,6',6a,6b,7,7',7'a,8,11,11a,11b-octadecahydro-3',6',10,11b-tetramethyl-, (2'R,3S,3'R,3'aS,6'S,6aS,6bS,7'aR,11aS,11bR)- (9CI); (3beta,22S,23R)-17,23-epoxyveratraman-3-ol; Veratraman-3-ol, 17,23-epoxy-, (3beta,23beta)-; CY8; [3H]-Cyclopamine; AC1L9DRQ; DSSTox_CID_23709; DSSTox_RID_80067; SCHEMBL29153

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 411.6
  Logarithm of the Partition Coefficient (xlogp); 3.5
  Rotatable Bond Count (rotbonds); 0
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 3
• Chemical Identifiers:
  Formula: C27H41NO2
  IUPAC Name: (3S,3'R,3'aS,6'S,6aS,6bS,7'aR,9R,11aS,11bR)-3',6',10,11b-tetramethylspiro[2,3,4,6,6a,6b,7,8,11,11a-decahydro-1H-benzo[a]fluorene-9,2'-3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine]-3-ol
  Canonical SMILES: C[C@H]1C[C@@H]2[C@H]([C@H]([C@]3(O2)CC[C@H]4[C@@H]5CC=C6C[C@H](CC[C@@]6([C@H]5CC4=C3C)C)O)C)NC1
  InChI: InChI=1S/C27H41NO2/c1-15-11-24-25(28-14-15)17(3)27(30-24)10-8-20-21-6-5-18-12-19(29)7-9-26(18,4)23(21)13-22(20)16(27)2/h5,15,17,19-21,23-25,28-29H,6-14H2,1-4H3/t15-,17+,19-,20-,21-,23-,24+,25-,26-,27-/m0/s1
  InChIKey: QASFUMOKHFSJGL-LAFRSMQTSA-N
• Cross-matching ID:
  PubChem CID: 442972
  ChEBI ID: CHEBI:4021
  CAS Number: 4449-51-8
  TTD ID: D05UKJ

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Smoothened homolog (SMO)	TT8J1S3	SMO_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Gene/Protein Processing	[2]
Arginase-1 (ARG1)	OTHZITAM	ARGI1_HUMAN	Gene/Protein Processing	[3]
G1/S-specific cyclin-E1 (CCNE1)	OTLD7UID	CCNE1_HUMAN	Drug Response	[4]
Insulin-like growth factor-binding protein 6 (IGFBP6)	OTW878VI	IBP6_HUMAN	Drug Response	[4]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Gene/Protein Processing	[3]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Gene/Protein Processing	[3]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Gene/Protein Processing	[3]
Macrophage mannose receptor 1 (MRC1)	OTTVCOPT	MRC1_HUMAN	Gene/Protein Processing	[3]
Neurogenic locus notch homolog protein 1 (NOTCH1)	OTI1WADQ	NOTC1_HUMAN	Protein Interaction/Cellular Processes	[5]
Nitric oxide synthase, inducible (NOS2)	OTKKIOJ1	NOS2_HUMAN	Gene/Protein Processing	[3]

Molecular Expression Atlas of This Drug

• The Studied Disease: Discovery agent
• ICD Disease Classification: N.A.

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Smoothened homolog (SMO)	DTT	SMO	4.01E-06	-0.18	-0.35

References

• [1] Identification and structure-activity relationships of ortho-biphenyl carboxamides as potent Smoothened antagonists inhibiting the Hedgehog signali... Bioorg Med Chem Lett. 2009 Jan 15;19(2):328-31.
• [2] Mono-2-ethyhexyl phthalate advancing the progression of prostate cancer through activating the hedgehog pathway in LNCaP cells. Toxicol In Vitro. 2016 Apr;32:86-91. doi: 10.1016/j.tiv.2015.12.012. Epub 2015 Dec 19.
• [3] M2 macrophage-derived IL6 mediates resistance of breast cancer cells to hedgehog inhibition. Toxicol Appl Pharmacol. 2019 Feb 1;364:77-82. doi: 10.1016/j.taap.2018.12.013. Epub 2018 Dec 19.
• [4] Response to inhibition of smoothened in diverse epithelial cancer cells that lack smoothened or patched 1 mutations. Int J Oncol. 2012 Nov;41(5):1751-61. doi: 10.3892/ijo.2012.1599. Epub 2012 Aug 22.
• [5] Effects of combination of notch inhibitor plus hedgehog inhibitor or Wnt inhibitor on growth of leukemia cells. Anticancer Res. 2011 Mar;31(3):893-6.