Details of the Drug

General Information of Drug (ID: DMLEDHR)

Drug Name
AL-43
Synonyms
AL-438; CHEMBL266282; A-240610.0; SCHEMBL4172433; BDBM50107347; A-224817.0; 5-Allyl-2,2,4-trimethyl-10-methoxy-2,5-dihydro-1H-1-aza-6-oxachrysene; 5-Allyl-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-6-oxa-1-aza-chrysene; 5-allyl-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-chromeno[3,4-f]quinoline; (+/-)5-Allyl-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-6-oxa-1-aza-chrysene; (+)5-Allyl-10-methoxy-2,2,4-trimethyl-2,5-dihydro-1H-6-oxa-1-aza-chrysene
Indication
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 347.4
Topological Polar Surface Area (xlogp) 5.1
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 3
Chemical Identifiers
Formula
C23H25NO2
IUPAC Name
10-methoxy-2,2,4-trimethyl-5-prop-2-enyl-1,5-dihydrochromeno[3,4-f]quinoline
Canonical SMILES
CC1=CC(NC2=C1C3=C(C=C2)C4=C(C=CC=C4OC)OC3CC=C)(C)C
InChI
InChI=1S/C23H25NO2/c1-6-8-18-22-15(21-17(25-5)9-7-10-19(21)26-18)11-12-16-20(22)14(2)13-23(3,4)24-16/h6-7,9-13,18,24H,1,8H2,2-5H3
InChIKey
CZSDJYXNNJQXBB-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
9906282
TTD ID
D0GR5L

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Androgen receptor messenger RNA (AR mRNA) TTKPW01 ANDR_HUMAN Inhibitor [1]
Glucocorticoid receptor messenger RNA (GCR mRNA) TTOZRK6 GCR_HUMAN Inhibitor [2]
Mineralocorticoid receptor (MR) TT26PHO MCR_HUMAN Inhibitor [1]
Progesterone receptor (PGR) TTUV8G9 PRGR_HUMAN Inhibitor [1]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

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
Glucocorticoid receptor messenger RNA (GCR mRNA) DTT NR3C1 3.19E-02 0.54 1.67
Mineralocorticoid receptor (MR) DTT NR3C2 7.31E-01 -5.31E-04 -1.53E-03
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 Nonsteroidal selective glucocorticoid modulators: the effect of C-10 substitution on receptor selectivity and functional potency of 5-allyl-2,5-dih... J Med Chem. 2003 Mar 13;46(6):1016-30.
2 Differentiation of in vitro transcriptional repression and activation profiles of selective glucocorticoid modulators. Bioorg Med Chem Lett. 2004 Apr 5;14(7):1721-7.
3 Clinical pipeline report, company report or official report of lipocine.
4 Preclinical experience with two selective progesterone receptor modulators on breast and endometrium. Steroids. 2000 Oct-Nov;65(10-11):733-40.
5 Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
6 Pharmacological profile of progestins. Maturitas. 2008 Sep-Oct;61(1-2):151-7.
7 Focus on anastrozole and breast cancer. Curr Med Res Opin. 2003;19(8):683-8.
8 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
9 Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharm... Steroids. 2008 Feb;73(2):222-31.
10 Contribution of functional groups of 19-nor-progestogens to binding to progesterone and estradiol-17beta receptors in rabbit uterus. Endocrinology. 1977 Jun;100(6):1579-84.
11 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
12 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
13 Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011).
14 Synthesis and activity of novel bile-acid conjugated glucocorticoid receptor antagonists. Bioorg Med Chem Lett. 2006 Dec 1;16(23):6086-90.
15 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.
16 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.
17 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.
18 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. (Target id: 628).
19 Synthesis and biological activity of a novel, highly potent progesterone receptor antagonist. J Med Chem. 2000 Dec 28;43(26):5010-6.
20 Clinical pipeline report, company report or official report of ISIS Pharmaceuticals.
21 2011 Pipeline of Santaris Pharma.
22 Effect of essential oils, such as raspberry ketone and its derivatives, on antiandrogenic activity based on in vitro reporter gene assay. Bioorg Med Chem Lett. 2010 Apr 1;20(7):2111-4.
23 Rational design and synthesis of 4-((1R,2R)-2-hydroxycyclohexyl)-2(trifluoromethyl)benzonitrile (PF-998425), a novel, nonsteroidal androgen recepto... J Med Chem. 2008 Nov 13;51(21):7010-4.
24 Effect of flavonoids on androgen and glucocorticoid receptors based on in vitro reporter gene assay. Bioorg Med Chem Lett. 2009 Aug 15;19(16):4706-10.
25 Stimulation of testosterone production in rat Leydig cells by aldosterone is mineralocorticoid receptor mediated. Mol Cell Endocrinol. 2005 Nov 24;243(1-2):35-42.
26 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
27 Mineralocorticoid receptor-mediated inhibition of the hypothalamic-pituitary-adrenal axis in aged humans. J Gerontol A Biol Sci Med Sci. 2003 Oct;58(10):B900-5.
28 Characterization of rat brain aldosterone receptors reveals high affinity for corticosterone. Endocrinology. 1983 Dec;113(6):2043-51.
29 Biochemical mechanisms of New Molecular Entities (NMEs) approved by United States FDA during 2001-2004: mechanisms leading to optimal efficacy and ... Curr Top Med Chem. 2006;6(5):461-78.
30 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
31 ZK91587: a novel synthetic antimineralocorticoid displays high affinity for corticosterone (type I) receptors in the rat hippocampus. Life Sci. 1988;43(19):1537-43.
32 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. (Target id: 626).