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

General Information of Drug (ID: DM5U1LN)

• Drug Name: aloisine A Drug Info
• Synonyms: ALOISINE A; 4-(7-butyl-5H-pyrrolo[2,3-b]pyrazin-6-yl)phenol; 496864-16-5; RP107; 6-PHENYL[5H]PYRROLO[2,3-B]PYRAZINE; CHEMBL75680; 7-n-Butyl-6-(4-hydroxyphenyl)[5H]pyrrolo[2,3-b]pyrazine; RP-107; ALH; 4-{7-butyl-5H-pyrrolo[2,3-b]pyrazin-6-yl}phenol; 1ung; SCHEMBL80147; BDBM7377; GTPL5924; AC1NS169; 4-(7-Butyl-5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenol; CHEBI:93641; CTK8D4068; DTXSID30416115; HMS3229A14; RM-39; BCP26893; ZINC2540737; ACT06534; IN1539; HSCI1_000219; MFCD04973541; AKOS005145972; CCG-206814; DB07364; RTC-063070; AJ-39131

Indication

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

• Cross-matching ID:
  PubChem CID: 448912
  ChEBI ID: CHEBI:93641
  CAS Number: CAS 496864-16-5
  TTD Drug ID: DM5U1LN

Molecule-Related Drug Atlas

Drug(s) Targeting G1/S-specific cyclin-E1 (CCNE1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PD-0183812	DMWYP86	Retinoblastoma	2D02.2	Terminated	[2]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	DMSKJ1X	Discovery agent	N.A.	Investigative	[3]
3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione	DMDO175	Discovery agent	N.A.	Investigative	[4]
3,4-diphenyl-1H-pyrrole-2,5-dione	DMPK6YT	Discovery agent	N.A.	Investigative	[4]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione	DMGC7RY	Discovery agent	N.A.	Investigative	[4]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[5]
3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione	DM3EV9N	Discovery agent	N.A.	Investigative	[4]
3-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol	DMJZK40	Discovery agent	N.A.	Investigative	[3]
(2'Z,3'E)-5-Chloro-5'-chloro-indirubin-3'-oxime	DMGXRSZ	Discovery agent	N.A.	Investigative	[6]
(2'Z,3'E)-5-Chloro-5'-methyl-indirubin-3'-oxime	DMZ0V6G	Discovery agent	N.A.	Investigative	[6]

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	[7]
Roscovitine derivative 1	DMD1G3Z	N. A.	N. A.	Patented	[8]
Tricyclic benzimidazole derivative 1	DM5SD9E	N. A.	N. A.	Patented	[8]
4-(thiazol-5-yl)-pyrimidine derivative 2	DMMQFCN	N. A.	N. A.	Patented	[8]
Pyrazolo[1,5-a]-1,3,5-triazine derivative 1	DMOK7CW	N. A.	N. A.	Patented	[8]
Naphthyridine and isoquinoline derivative 1	DMTGIP7	N. A.	N. A.	Patented	[8]
PMID26161698-Compound-18	DM6JVR5	N. A.	N. A.	Patented	[8]
Flavonoid derivative 7	DM6A9UR	N. A.	N. A.	Patented	[8]
L-751250	DMOERXK	Obesity	5B81	Preclinical	[9]
Olomoucine	DMNAFG1	N. A.	N. A.	Terminated	[9]

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	[10]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]
P276-00	DM9DJL2	Mantle cell lymphoma	2A85.5	Phase 2	[10]
P-276	DMMJUHD	Breast cancer	2C60-2C65	Phase 2	[12]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[13]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
Oxazolyl methylthiothiazole derivative 1	DMZM6FW	N. A.	N. A.	Patented	[8]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[15]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[16]

Drug(s) Targeting Cyclin A2 (CCNA2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PD-0183812	DMWYP86	Retinoblastoma	2D02.2	Terminated	[2]
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	DMSKJ1X	Discovery agent	N.A.	Investigative	[3]
3-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol	DMJZK40	Discovery agent	N.A.	Investigative	[3]
MERIOLIN 8	DM0E95B	Discovery agent	N.A.	Investigative	[17]
2,5-dichloro-N-p-tolylthiophene-3-sulfonamide	DMU5J8Y	Discovery agent	N.A.	Investigative	[18]
Purvalanol A	DMNQ7TM	Discovery agent	N.A.	Investigative	[19]
MERIOLIN 1	DMJT93H	Discovery agent	N.A.	Investigative	[17]
MERIOLIN 4	DMIJMZQ	Discovery agent	N.A.	Investigative	[17]
MERIOLIN 6	DMW5AXC	Discovery agent	N.A.	Investigative	[17]
MERIOLIN 5	DMGVLR0	Discovery agent	N.A.	Investigative	[17]

Drug(s) Targeting Cyclin-dependent kinase 2 (CDK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
R-roscovitine	DMSH108	Non-small-cell lung cancer	2C25.Y	Phase 2	[10]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[11]
PHA848125	DMS2Q9G	Thymic cancer	2C27	Phase 2	[20]
TG02	DMZFIGQ	Anaplastic astrocytoma	2A00.0	Phase 1/2	[21]
NUV-422	DMQJQNT	Malignant glioma	2A00.0	Phase 1/2	[22]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[13]
FN-1501	DM7BMD6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[23]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[14]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[24]

Drug(s) Targeting GSK3A messenger RNA (GSK3A mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CHIR-98014	DMVEBT6	Discovery agent	N.A.	Investigative	[25]
indirubin deriv. 8a	DMYLVQF	Discovery agent	N.A.	Investigative	[26]
LEUCETTAMINE B	DMFQEWM	Discovery agent	N.A.	Investigative	[27]
ISIS 116625	DMIJES1	Discovery agent	N.A.	Investigative	[28]
ISIS 116648	DMUOB3S	Discovery agent	N.A.	Investigative	[28]
ISIS 116632	DMW2Q4T	Discovery agent	N.A.	Investigative	[28]
ISIS 116631	DM2X5RT	Discovery agent	N.A.	Investigative	[28]
ISIS 116670	DM9R51M	Discovery agent	N.A.	Investigative	[28]
ISIS 116654	DMBJU2X	Discovery agent	N.A.	Investigative	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cyclin A2 (CCNA2)	TTAMQ62	CCNA2_HUMAN	Inhibitor	[1]
Cyclin-dependent kinase 1 (CDK1)	TTH6V3D	CDK1_HUMAN	Inhibitor	[1]
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[1]
Cyclin-dependent kinase 5 (CDK5)	TTL4Q97	CDK5_HUMAN	Inhibitor	[1]
G1/S-specific cyclin-E1 (CCNE1)	TTCEJ4F	CCNE1_HUMAN	Inhibitor	[1]
GSK3A messenger RNA (GSK3A mRNA)	TTQWAU1	GSK3A_HUMAN	Inhibitor	[1]

References

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• [2] Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. J Med Chem. 2000 Nov 30;43(24):4606-16.
• [3] 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9.
• [4] Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81.
• [5] Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitum... J Med Chem. 2005 Sep 8;48(18):5639-43.
• [6] 5,5'-substituted indirubin-3'-oxime derivatives as potent cyclin-dependent kinase inhibitors with anticancer activity. J Med Chem. 2010 May 13;53(9):3696-706.
• [7] 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
• [8] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [9] Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol Sci. 2002 Sep;23(9):417-25.
• [10] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [16] 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.
• [17] Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolin com... J Med Chem. 2008 Feb 28;51(4):737-51.
• [18] Activity of substituted thiophene sulfonamides against malarial and mammalian cyclin dependent protein kinases, Bioorg. Med. Chem. Lett. 20(13):3863-3867 (2010).
• [19] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [20] Identification of N,1,4,4-tetramethyl-8-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide (PHA-848125), a potent, orally available cyclin dependent kinase inhibitor. J Med Chem. 2009 Aug 27;52(16):5152-63.
• [21] Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
• [22] ClinicalTrials.gov (NCT04541225) Phase 1/2 Dose Escalation, Safety, Pharmacokinetics, and Efficacy Study of NUV-422 in Adults With Recurrent or Refractory High-grade Gliomas and Solid Tumors. U.S.National Institutes of Health.
• [23] Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin-1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia. J Med Chem. 2018 Feb 22;61(4):1499-1518.
• [24] Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.
• [25] 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.
• [26] Structural basis for the synthesis of indirubins as potent and selective inhibitors of glycogen synthase kinase-3 and cyclin-dependent kinases. J Med Chem. 2004 Feb 12;47(4):935-46.
• [27] Synthesis and preliminary biological evaluation of new derivatives of the marine alkaloid leucettamine B as kinase inhibitors. Eur J Med Chem. 2010 Feb;45(2):805-10.
• [28] US patent application no. 6,316,259, Antisense inhibition of glycogen synthase kinase 3 alpha expression.