Details of the Drug

General Information of Drug (ID: DM9SKW8)

Drug Name

AZD5363

Synonyms

AZD5363; 1143532-39-1; AZD-5363; capivasertib; AZD 5363; UNII-WFR23M21IE; WFR23M21IE; cc-638; 4-Amino-N-[(1s)-1-(4-Chlorophenyl)-3-Hydroxypropyl]-1-(7h-Pyrrolo[2,3-D]pyrimidin-4-Yl)piperidine-4-Carboxamide; C21H25ClN6O2; (S)-4-AMINO-N-(1-(4-CHLOROPHENYL)-3-HYDROXYPROPYL)-1-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)PIPERIDINE-4-CARBOXAMIDE; 4-Amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidinecarboxamide; 4-Piperidinecarboxamide, 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1

Indication

Disease Entry	ICD 11	Status	REF
Triple negative breast cancer	2C60-2C65	Phase 3	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[2], [3]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

428.9

Topological Polar Surface Area (xlogp)

1.7

Rotatable Bond Count (rotbonds)

6

Hydrogen Bond Donor Count (hbonddonor)

4

Hydrogen Bond Acceptor Count (hbondacc)

6

Chemical Identifiers

Formula: C21H25ClN6O2
IUPAC Name: 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide
Canonical SMILES: C1CN(CCC1(C(=O)N[C@@H](CCO)C2=CC=C(C=C2)Cl)N)C3=NC=NC4=C3C=CN4
InChI: InChI=1S/C21H25ClN6O2/c22-15-3-1-14(2-4-15)17(6-12-29)27-20(30)21(23)7-10-28(11-8-21)19-16-5-9-24-18(16)25-13-26-19/h1-5,9,13,17,29H,6-8,10-12,23H2,(H,27,30)(H,24,25,26)/t17-/m0/s1
InChIKey: JDUBGYFRJFOXQC-KRWDZBQOSA-N

Cross-matching ID

PubChem CID: 25227436
CAS Number: 1143532-39-1
DrugBank ID: DB12218
TTD ID: D01ZAQ

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
RAC-alpha serine/threonine-protein kinase (AKT1)	TTWTSCV	AKT1_HUMAN	Inhibitor	[4]
RAC-gamma serine/threonine-protein kinase (AKT3)	TTAZ05C	AKT3_HUMAN	Modulator	[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

Triple negative breast cancer

ICD Disease Classification

2C60-2C65

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
RAC-alpha serine/threonine-protein kinase (AKT1)	DTT	AKT1	2.63E-29	0.65	1.45
RAC-gamma serine/threonine-protein kinase (AKT3)	DTT	AKT3	6.79E-01	-0.02	-0.08

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	ClinicalTrials.gov (NCT03997123) Capivasertib+Paclitaxel as First Line Treatment for Patients With Locally Advanced or Metastatic TNBC (CAPItello-290). U.S. National Institutes of Health.
2	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: 7709).
3	ClinicalTrials.gov (NCT02077569) AKT Inhibitor in Oestrogen Positive Breast Cancer. U.S. National Institutes of Health.
4	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5	The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma. Blood. 2014 Oct 2;124(14):2190-5.
6	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.
7	Pre-clinical and Clinical Safety Studies of CMX-2043: a cytoprotective lipoic acid analogue for ischaemia-reperfusion injury. Basic Clin Pharmacol Toxicol. 2014 Nov;115(5):456-64.
8	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
9	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: 1479).
10	CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
11	Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
12	First-in-man clinical trial of the oral pan-AKT inhibitor MK-2206 in patients with advanced solid tumors.J Clin Oncol.2011 Dec 10;29(35):4688-95.
13	Inhibiting the akt pathway in cancer treatment: three leading candidates. P T. 2011 Apr;36(4):225-7.
14	DOI: 10.1016/S1359-6349(10)71767-5
15	A first-in-human phase I trial of LY2780301, a dual p70 S6 kinase and Akt Inhibitor, in patients with advanced or metastatic cancer. Invest New Drugs. 2015 Jun;33(3):710-9.
16	Targeting the phosphoinositide 3-kinase (PI3K) pathway in cancer
17	Phase 0 clinical chemoprevention trial of the Akt inhibitor SR13668. Cancer Prev Res (Phila). 2011 Mar;4(3):347-53.
18	Phase I pharmacokinetic and pharmacodynamic study of triciribine phosphate monohydrate, a small-molecule inhibitor of AKT phosphorylation, in adult subjects with solid tumors containing activated AKT.Invest New Drugs.2011 Dec;29(6):1381-9.
19	Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity.Cancer Res.2008 Apr 1;68(7):2366-74.