Details of the Drug

General Information of Drug (ID: DMJ3ZT8)

Drug Name

Lexacalcitol

Synonyms

KH-106; KH-1060; MC-1357; Vitamin D3 agonist, Leo

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 2	[1]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

460.7

Logarithm of the Partition Coefficient (xlogp)

4.9

Rotatable Bond Count (rotbonds)

9

Hydrogen Bond Donor Count (hbonddonor)

3

Hydrogen Bond Acceptor Count (hbondacc)

4

Chemical Identifiers

Formula: C29H48O4
IUPAC Name: (1R,3S,5Z)-5-[(2E)-2-[(1S,3aS,7aS)-1-[(1R)-1-(4-ethyl-4-hydroxyhexoxy)ethyl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
Canonical SMILES: CCC(CC)(CCCO[C@H](C)[C@H]1CC[C@@H]\\2[C@@]1(CCC/C2=C\\C=C/3\\C[C@H](C[C@@H](C3=C)O)O)C)O
InChI: InChI=1S/C29H48O4/c1-6-29(32,7-2)16-9-17-33-21(4)25-13-14-26-22(10-8-15-28(25,26)5)11-12-23-18-24(30)19-27(31)20(23)3/h11-12,21,24-27,30-32H,3,6-10,13-19H2,1-2,4-5H3/b22-11+,23-12-/t21-,24-,25-,26+,27+,28-/m1/s1
InChIKey: KLZOTDOJMRMLDX-YBBVPDDNSA-N

Cross-matching ID

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cathelicidin antimicrobial peptide (CAMP)	OT3Y8011	CAMP_HUMAN	Gene/Protein Processing	[3]
Cyclin-dependent kinase 2 (CDK2)	OTB5DYYZ	CDK2_HUMAN	Gene/Protein Processing	[4]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Gene/Protein Processing	[4]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Gene/Protein Processing	[4]
G1/S-specific cyclin-E1 (CCNE1)	OTLD7UID	CCNE1_HUMAN	Gene/Protein Processing	[4]
Osteocalcin (BGLAP)	OTK1YLWQ	OSTCN_HUMAN	Gene/Protein Processing	[5]
Retinoblastoma-associated protein (RB1)	OTQJUJMZ	RB_HUMAN	Post-Translational Modifications	[4]
Vitamin D3 receptor	OTFC7K35	VDR_HUMAN	Protein Interaction/Cellular Processes	[6]

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Molecular Interaction Atlas (MIA)

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Solid tumour/cancer

ICD Disease Classification

2A00-2F9Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Vitamin D3 receptor (VDR)	DTT	VDR	1.69E-02	-0.23	-0.66

Molecular Expression Atlas (MEA)

Jump to Detail Molecular Expression Atlas of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2775).
2	The vitamin D analog, KH1060, is rapidly degraded both in vivo and in vitro via several pathways: principal metabolites generated retain significant biological activity. Endocrinology. 1997 Dec;138(12):5485-96.
3	Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J. 2005 Jul;19(9):1067-77. doi: 10.1096/fj.04-3284com.
4	Inhibition of MG-63 cell cycle progression by synthetic vitamin D3 analogs mediated by p27, Cdk2, cyclin E, and the retinoblastoma protein. Biochem Pharmacol. 2003 Aug 1;66(3):495-504. doi: 10.1016/s0006-2952(03)00283-1.
5	9-cis retinoic acid accelerates calcitriol-induced osteocalcin production and promotes degradation of both vitamin D receptor and retinoid X receptor in human osteoblastic cells. J Cell Biochem. 2003 Aug 15;89(6):1164-76. doi: 10.1002/jcb.10572.
6	Targacept active conformation search: a new method for predicting the conformation of a ligand bound to its protein target. J Med Chem. 2004 Dec 30;47(27):6831-9.