Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM61H07)

• Drug Name: AZAKENPAULLONE Drug Info
• Synonyms: 1-Azakenpaullone; 676596-65-9; azakenpaullone; 9-bromo-7,12-dihydropyrido[3',2':2,3]azepino[4,5-b]indol-6(5H)-one; C15H10BrN3O; Kinome_3492; 1-AKP; SCHEMBL378920; GTPL8018; CHEMBL336961; BDBM7497; DTXSID8042686; NOCAS_42686; CTK8F0375; MolPort-003-844-675; CHEBI:131490; HMS3653A17; HMS3229B07; BCP21061; ZINC13588927; s7193; 2138AH; 1-Azakenpaullone, > AKOS030240424; SB19270; TRA0006688; NCGC00386322-01; RT-006179; FT-0662368; SW220021-1; KS-00001866

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 6538897
  ChEBI ID: CHEBI:131490
  TTD Drug ID: DM61H07

Molecule-Related Drug Atlas

Drug(s) Targeting Cyclin-dependent kinase 5 (CDK5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[2]
Roscovitine derivative 1	DMD1G3Z	N. A.	N. A.	Patented	[3]
Tricyclic benzimidazole derivative 1	DM5SD9E	N. A.	N. A.	Patented	[3]
4-(thiazol-5-yl)-pyrimidine derivative 2	DMMQFCN	N. A.	N. A.	Patented	[3]
Pyrazolo[1,5-a]-1,3,5-triazine derivative 1	DMOK7CW	N. A.	N. A.	Patented	[3]
Naphthyridine and isoquinoline derivative 1	DMTGIP7	N. A.	N. A.	Patented	[3]
PMID26161698-Compound-18	DM6JVR5	N. A.	N. A.	Patented	[3]
Flavonoid derivative 7	DM6A9UR	N. A.	N. A.	Patented	[3]
L-751250	DMOERXK	Obesity	5B81	Preclinical	[4]
Olomoucine	DMNAFG1	N. A.	N. A.	Terminated	[4]

Drug(s) Targeting Cyclin-dependent kinase 1 (CDK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
R-roscovitine	DMSH108	Non-small-cell lung cancer	2C25.Y	Phase 2	[5]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[6]
P276-00	DM9DJL2	Mantle cell lymphoma	2A85.5	Phase 2	[5]
P-276	DMMJUHD	Breast cancer	2C60-2C65	Phase 2	[7]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[8]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
Oxazolyl methylthiothiazole derivative 1	DMZM6FW	N. A.	N. A.	Patented	[3]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[10]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[11]

Drug(s) Targeting Glycogen synthase kinase-3 beta (GSK-3B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AMO-02	DMJRU3A	Myotonic dystrophy	8C71.0	Phase 2/3	[12]
LY2090314	DMTBFE4	Acute myeloid leukaemia	2A60	Phase 2	[13]
Lithium	DMZ3OU6	Fragile X syndrome	LD55	Phase 2	[14]
Tideglusib	DME4LA1	Osteosarcoma	2B51	Phase 2	[15]
9-ING-41	DM57TY3	Myelofibrosis	2A20.2	Phase 2	[16]
Neu-120	DMXKOUC	Parkinson disease	8A00.0	Phase 1/2	[17]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[2]
CHIR-99021	DMB8MNU	Allergic inflammation	4A80-4A85	Patented	[18]
TDZD-8	DMG6Q45	Malignant glioma	2A00.0	Patented	[19]
AR-A014418	DMUPN01	Ovarian cancer	2C73	Patented	[20]

Drug(s) Targeting G2/mitotic-specific cyclin B1 (CCNB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[11]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[21]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[21]
3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione	DMDO175	Discovery agent	N.A.	Investigative	[22]
3,4-diphenyl-1H-pyrrole-2,5-dione	DMPK6YT	Discovery agent	N.A.	Investigative	[22]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione	DMGC7RY	Discovery agent	N.A.	Investigative	[22]
3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione	DM3EV9N	Discovery agent	N.A.	Investigative	[22]
Thieno analogue of kenpaullone	DMIOTHG	Discovery agent	N.A.	Investigative	[2]
3,4-bis(indol-3-yl)maleimide derivative	DMEQ1HC	Discovery agent	N.A.	Investigative	[21]
4-(Quinolin-4-yl)-N-p-tolylpyrimidin-2-amine	DMDW3SX	Discovery agent	N.A.	Investigative	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cyclin-dependent kinase 1 (CDK1)	TTH6V3D	CDK1_HUMAN	Inhibitor	[2]
Cyclin-dependent kinase 5 (CDK5)	TTL4Q97	CDK5_HUMAN	Inhibitor	[2]
G2/mitotic-specific cyclin B1 (CCNB1)	TT9P6OW	CCNB1_HUMAN	Inhibitor	[2]
Glycogen synthase kinase-3 beta (GSK-3B)	TTRSMW9	GSK3B_HUMAN	Inhibitor	[2]

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: 8018).
• [2] 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
• [3] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [4] Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci. 2002 Sep;23(9):417-25.
• [5] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [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] P276-00, a novel cyclin-dependent inhibitor induces G1-G2 arrest, shows antitumor activity on cisplatin-resistant cells and significant in vivo efficacy in tumor models. Mol Cancer Ther. 2007 Mar;6(3):926-34.
• [8] Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia. 2013 Dec;27(12):2366-75.
• [9] A first in man, phase I dose-escalation study of PHA-793887, an inhibitor of multiple cyclin-dependent kinases (CDK2, 1 and 4) reveals unexpected h... Cell Cycle. 2011 Mar 15;10(6):963-70.
• [10] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [11] Discovery of novel CDK1 inhibitors by combining pharmacophore modeling, QSAR analysis and in silico screening followed by in vitro bioassay. Eur J Med Chem. 2010 Sep;45(9):4316-30.
• [12] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [13] Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
• [14] The GSK3 kinase inhibitor lithium produces unexpected hyperphosphorylation of -catenin, a GSK3 substrate, in human glioblastoma cells. Biol Open. 2018 Jan 26;7(1):bio030874.
• [15] Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
• [16] 9-ING-41, a small molecule inhibitor of GSK-3beta, potentiates the effects of anticancer therapeutics in bladder cancer. Sci Rep. 2019 Dec 27;9(1):19977.
• [17] Company report (Neurim Pharmaceuticals)
• [18] Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.
• [19] Identification of novel scaffold of benzothiazepinones as non-ATP competitive glycogen synthase kinase-3beta inhibitors through virtual screening. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7232-6.
• [20] Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
• [21] Design of new inhibitors for cdc2 kinase based on a multiple pseudosubstrate structure. Bioorg Med Chem Lett. 1998 May 5;8(9):1019-22.
• [22] Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81.
• [23] Synthesis and cytotoxic activity of 2-methylimidazo[1,2-a]pyridine- and quinoline-substituted 2-aminopyrimidine derivatives. Eur J Med Chem. 2010 Jan;45(1):379-86.