Details of the Drug

General Information of Drug (ID: DM25CBW)

Drug Name

A-348441

Synonyms

A-348441; CHEMBL219684; SCHEMBL699533; BDBM50195155; KB-3305

Indication

Disease Entry	ICD 11	Status	REF
Type-2 diabetes	5A11	Phase 1	[1]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 3

Molecular Weight (mw)

850.2

Topological Polar Surface Area (xlogp)

7.7

Rotatable Bond Count (rotbonds)

11

Hydrogen Bond Donor Count (hbonddonor)

4

Hydrogen Bond Acceptor Count (hbondacc)

8

Chemical Identifiers

Formula: C54H75NO7
IUPAC Name: (4R)-4-[(3S,5R,7R,8R,9S,10S,12S,13R,14S,17R)-7,12-dihydroxy-3-[2-[4-[(8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-prop-1-ynyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-11-yl]-N-methylanilino]ethoxy]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid
Canonical SMILES: CC#C[C@@]1(CC[C@@H]2[C@@]1(C[C@@H](C3=C4CCC(=O)C=C4CC[C@@H]23)C5=CC=C(C=C5)N(C)CCO[C@H]6CC[C@]7([C@@H](C6)C[C@H]([C@@H]8[C@@H]7C[C@@H]([C@]9([C@H]8CC[C@@H]9[C@H](C)CCC(=O)O)C)O)O)C)C)O
InChI: InChI=1S/C54H75NO7/c1-7-22-54(61)24-21-43-40-15-11-34-27-37(56)14-16-39(34)49(40)41(31-52(43,54)4)33-9-12-36(13-10-33)55(6)25-26-62-38-20-23-51(3)35(28-38)29-46(57)50-44-18-17-42(32(2)8-19-48(59)60)53(44,5)47(58)30-45(50)51/h9-10,12-13,27,32,35,38,40-47,50,57-58,61H,8,11,14-21,23-26,28-31H2,1-6H3,(H,59,60)/t32-,35+,38+,40+,41-,42-,43+,44+,45+,46-,47+,50+,51+,52+,53-,54+/m1/s1
InChIKey: LEUWECPXLBIBOF-NZWIZOFBSA-N

Cross-matching ID

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Glucocorticoid receptor messenger RNA (GCR mRNA)	TTOZRK6	GCR_HUMAN	Inhibitor	[2]

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Molecular Interaction Atlas (MIA)

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Molecular Expression Atlas of This Drug

The Studied Disease

Type-2 diabetes

ICD Disease Classification

5A11

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Glucocorticoid receptor messenger RNA (GCR mRNA)	DTT	NR3C1	3.19E-02	0.54	1.67

Molecular Expression Atlas (MEA)

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References

1	Liver-selective glucocorticoid receptor antagonism decreases glucose production and increases glucose disposal, ameliorating insulin resistance. Metabolism. 2007 Mar;56(3):380-7.
2	Synthesis and activity of novel bile-acid conjugated glucocorticoid receptor antagonists. Bioorg Med Chem Lett. 2006 Dec 1;16(23):6086-90.
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5	Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011).
6	Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.
7	Functional probing of the human glucocorticoid receptor steroid-interacting surface by site-directed mutagenesis. Gln-642 plays an important role in steroid recognition and binding. J Biol Chem. 2000Jun 23;275(25):19041-9.
8	Antiinflammatory glucocorticoid receptor ligand with reduced side effects exhibits an altered protein-protein interaction profile. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19244-9.
9	Differentiation of in vitro transcriptional repression and activation profiles of selective glucocorticoid modulators. Bioorg Med Chem Lett. 2004 Apr 5;14(7):1721-7.