Details of the Drug

General Information of Drug (ID: DMQF982)

Drug Name

AEW-541

Synonyms

AECDBHGVIIRMOI-UHFFFAOYSA-N; NVP-AEW541; 475489-16-8; 475488-34-7; AEW541; NVP-AEW 541; UNII-97QB5037VR; AEW 541; AVP-AEW541; 7-((1s,3s)-3-(azetidin-1-ylmethyl)cyclobutyl)-5-(3-(benzyloxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine; CHEMBL1614712; 97QB5037VR; 7-[TRANS-3-(1-AZETIDINYLMETHYL)CYCLOBUTYL]-5-[3-(PHENYLMETHOXY)PHENYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE; C27H29N5O; 7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE, 7-[CIS-3-(1-AZETIDINYLMETHYL)CYCLOBUTYL]-5-[3-(PHENYLMETHOXY)PHENYL]-

Indication

Disease Entry	ICD 11	Status	REF
Multiple myeloma	2A83	Phase 1	[1]

Therapeutic Class

Anticancer Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

439.6

Topological Polar Surface Area (xlogp)

4.2

Rotatable Bond Count (rotbonds)

7

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

5

Chemical Identifiers

Formula: C27H29N5O
IUPAC Name: 7-[3-(azetidin-1-ylmethyl)cyclobutyl]-5-(3-phenylmethoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine
Canonical SMILES: C1CN(C1)CC2CC(C2)N3C=C(C4=C(N=CN=C43)N)C5=CC(=CC=C5)OCC6=CC=CC=C6
InChI: InChI=1S/C27H29N5O/c28-26-25-24(21-8-4-9-23(14-21)33-17-19-6-2-1-3-7-19)16-32(27(25)30-18-29-26)22-12-20(13-22)15-31-10-5-11-31/h1-4,6-9,14,16,18,20,22H,5,10-13,15,17H2,(H2,28,29,30)
InChIKey: AECDBHGVIIRMOI-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 11476171
CAS Number: 475488-34-7
TTD ID: D07HPJ

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Insulin receptor (INSR)	TTCBFJO	INSR_HUMAN	Inhibitor	[2]
Insulin-like growth factor I receptor (IGF1R)	TTHRID2	IGF1R_HUMAN	Inhibitor	[3], [4], [5]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Multiple myeloma

ICD Disease Classification

2A83

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Insulin receptor (INSR)	DTT	INSR	1.03E-05	0.26	0.66

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019974)
2	Inhibition of the insulin-like growth factor-1 receptor (IGF1R) tyrosine kinase as a novel cancer therapy approach. J Med Chem. 2009 Aug 27;52(16):4981-5004.
3	A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
4	Co-targeting the EGFR and IGF-IR with anti-EGFR monoclonal antibody ICR62 and the IGF-IR tyrosine kinase inhibitor NVP-AEW541 in colorectal cancer cells. Int J Oncol. 2008 Nov;33(5):1107-13.
5	FAK and IGF-IR interact to provide survival signals in human pancreatic adenocarcinoma cells. Carcinogenesis. 2008 Jun;29(6):1096-107.
6	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
7	IGF-1R, IGF-1 and IGF-2 expression as potential prognostic and predictive markers in colorectal-cancer. Virchows Arch. 2003 Aug;443(2):139-45.
8	2005 approvals: Safety first. Nature Reviews Drug Discovery 5, 92-93 (February 2006).
9	Imidazo[2,1-b]thiazoles: multitargeted inhibitors of both the insulin-like growth factor receptor and members of the epidermal growth factor family... Bioorg Med Chem Lett. 2010 Apr 15;20(8):2452-5.
10	Mecasermin rinfabate: insulin-like growth factor-I/insulin-like growth factor binding protein-3, mecaserimin rinfibate, rhIGF-I/rhIGFBP-3. Drugs R D. 2005;6(2):120-7.
11	MM-141, an IGF-IR- and ErbB3-directed bispecific antibody, overcomes network adaptations that limit activity of IGF-IR inhibitors. Mol Cancer Ther. 2014 Feb;13(2):410-25.
12	BiPar Sciences Co-founder Reunites Management Team At TriAct Therapeutics to Advance Clinical Stage Cancer Programs. TriAct Therapeutics. Sept. 10, 2009.
13	Clinical pipeline report, company report or official report of Amgen (2009).
14	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
15	Clinical Phase I study with an Insulin-like Growth Factor-1 receptor inhibitor: experiences in patients with squamous non-small cell lung carcinoma. Acta Oncol. 2011 Apr;50(3):441-7.
16	New drugs for type 2 diabetes mellitus: what is their place in therapy Drugs. 2008;68(15):2131-62.
17	Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
18	Acidic residues on the N-terminus of proinsulin C-Peptide are important for the folding of insulin precursor. J Biochem. 2002 Jun;131(6):855-9.
19	Metformin (Glucophage) inhibits tyrosine phosphatase activity to stimulate the insulin receptor tyrosine kinase. Biochem Pharmacol. 2004 Jun 1;67(11):2081-91.
20	Hope for insulin mimetic oral antidiabetic drugs. Eur J Endocrinol. 1999 Dec;141(6):561-2.
21	Insulin glulisine: a review of its use in the management of diabetes mellitus. Drugs. 2009;69(8):1035-57.
22	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: 1800).