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

General Information of Drug (ID: DM32FKD)

• Drug Name: PF-228 Drug Info
• Synonyms: 869288-64-2; PF-573228; PF 573228; PF573228; PF-228; CHEMBL514554; 3,4-Dihydro-6-[[4-[[[3-(methylsulfonyl)phenyl]methyl]amino]-5-(trifluoromethyl)-2-pyrimidinyl]amino]-2(1H)-quinolinone; 6-((4-((3-(Methylsulfonyl)benzyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3,4-dihydroquinolin-2(1H)-one; 6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one; 6-[4-(3-Methanesulfonyl-benzylamino)-5-trifluoromethyl-pyrimidin-2-ylamino]-3,4-dihydro-1H-quinolin-2-one

Indication

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

• Cross-matching ID:
  PubChem CID: 11612883
  ChEBI ID: CHEBI:91446
  CAS Number: CAS 869288-64-2
  TTD Drug ID: DM32FKD

Molecule-Related Drug Atlas

Drug(s) Targeting Focal adhesion kinase 1 (FAK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VS-6063	DMGBLI3	Mesothelioma	2C51.2	Phase 2	[2]
BI-853520	DMNOSYW	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
PF-562271	DMSLE03	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
VS-4718	DMN9JCD	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
GSK-2256098	DMR24MI	Pulmonary arterial hypertension	BB01.0	Phase 1	[6]
CEP-37440	DMV632P	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]
IN10018	DMPXOVA	Metastatic melanoma	2E2Z	Phase 1	[7]
1,2,4-triazolo[1,5a]pyridine derivative 1	DMIUPSA	N. A.	N. A.	Patented	[8]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[9]
PMID23414845C30	DMNVQ29	Discovery agent	N.A.	Investigative	[10]

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	[11]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]
P276-00	DM9DJL2	Mantle cell lymphoma	2A85.5	Phase 2	[11]
P-276	DMMJUHD	Breast cancer	2C60-2C65	Phase 2	[13]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[14]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[15]
Oxazolyl methylthiothiazole derivative 1	DMZM6FW	N. A.	N. A.	Patented	[16]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[17]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[18]

Drug(s) Targeting Cyclin-dependent kinase 7 (CDK7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
R-roscovitine	DMSH108	Non-small-cell lung cancer	2C25.Y	Phase 2	[11]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[19]
BTX-A51	DMC8XHQ	Advanced solid tumour	2A00-2F9Z	Phase 1	[20]
SY-1365	DMK48PM	Solid tumour/cancer	2A00-2F9Z	Phase 1	[21]
LY3405105	DMB51K2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[22]
SY-5609	DMNW3LH	Solid tumour/cancer	2A00-2F9Z	Phase 1	[23]
Oxazolyl methylthiothiazole derivative 1	DMZM6FW	N. A.	N. A.	Patented	[16]
Roscovitine derivative 1	DMD1G3Z	N. A.	N. A.	Patented	[16]
Tricyclic benzimidazole derivative 1	DM5SD9E	N. A.	N. A.	Patented	[16]
Pyrazolo-triazine derivative 2	DML6V78	N. A.	N. A.	Patented	[16]

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	[11]
Ro 31-7453	DM83QCL	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]
PHA848125	DMS2Q9G	Thymic cancer	2C27	Phase 2	[24]
TG02	DMZFIGQ	Anaplastic astrocytoma	2A00.0	Phase 1/2	[25]
RGB-286638	DMEGOQP	Haematological malignancy	2B33.Y	Phase 1	[14]
FN-1501	DM7BMD6	Solid tumour/cancer	2A00-2F9Z	Phase 1	[26]
AG-024322	DMY4WVK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[11]
PHA-793887	DM2Y4FG	Solid tumour/cancer	2A00-2F9Z	Phase 1	[15]
SNS-032	DMEITAS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[19]
CYC065	DM9ODT6	Lymphoma	2A80-2A86	Phase 1	[21]

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	[27]
LY2090314	DMTBFE4	Acute myeloid leukaemia	2A60	Phase 2	[28]
Lithium	DMZ3OU6	Fragile X syndrome	LD55	Phase 2	[29]
Tideglusib	DME4LA1	Osteosarcoma	2B51	Phase 2	[30]
9-ING-41	DM57TY3	Myelofibrosis	2A20.2	Phase 2	[31]
Neu-120	DMXKOUC	Parkinson disease	8A00.0	Phase 1/2	[32]
KENPAULLONE	DMAGVXW	Discovery agent	N.A.	Patented	[33]
CHIR-99021	DMB8MNU	Allergic inflammation	4A80-4A85	Patented	[34]
TDZD-8	DMG6Q45	Malignant glioma	2A00.0	Patented	[35]
AR-A014418	DMUPN01	Ovarian cancer	2C73	Patented	[36]

Drug(s) Targeting Inhibitor of nuclear factor kappa-B kinase beta (IKKB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[37]
Parthenolide	DMCQBFT	N. A.	N. A.	Phase 2	[38]
SAR-113945	DMMCA9V	Osteoarthritis	FA00-FA05	Phase 2	[39]
IMD-1041	DMU1MR9	Alzheimer disease	8A20	Phase 2	[40]
IMD-0354	DMOFSLE	Acne vulgaris	ED80	Phase 1	[41]
MLN0415	DMG72VK	Arthritis	FA20	Discontinued in Phase 1	[42]
5-Bromo-6-methoxy-9H-beta-carboline	DM157OQ	Discovery agent	N.A.	Investigative	[43]
Staurosporine	DM0E9BR	Discovery agent	N.A.	Investigative	[44]
5-amino-2-phenyl-oxazole-4-carboxylic acid amide	DMX37ZC	Discovery agent	N.A.	Investigative	[45]
5-amino-2-p-tolyl-oxazole-4-carboxylic acid amide	DM4SWJ7	Discovery agent	N.A.	Investigative	[45]

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	[1]
Cyclin-dependent kinase 2 (CDK2)	TT7HF4W	CDK2_HUMAN	Inhibitor	[1]
Cyclin-dependent kinase 7 (CDK7)	TTQYF7G	CDK7_HUMAN	Inhibitor	[1]
Focal adhesion kinase 1 (FAK)	TTON5IT	FAK1_HUMAN	Inhibitor	[1]
Glycogen synthase kinase-3 beta (GSK-3B)	TTRSMW9	GSK3B_HUMAN	Inhibitor	[1]
Inhibitor of nuclear factor kappa-B kinase beta (IKKB)	TTJ3E9X	IKKB_HUMAN	Inhibitor	[1]

References

• [1] Cellular characterization of a novel focal adhesion kinase inhibitor. J Biol Chem. 2007 May 18;282(20):14845-52.
• [2] Role of focal adhesion kinase in regulating YB-1-mediated paclitaxel resistance in ovarian cancer. J Natl Cancer Inst. 2013 Oct 2;105(19):1485-95.
• [3] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [4] Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and metastasis of pancreatic cancer concomitant with altering the tumor microenvironment. Mol Cancer Ther. 2011 Nov;10(11):2135-45.
• [5] FAK Inhibition disrupts a beta5 integrin signaling axis controlling anchorage-independent ovarian carcinoma growth. Mol Cancer Ther. 2014 Aug;13(8):2050-61.
• [6] A small molecule FAK kinase inhibitor, GSK2256098, inhibits growth and survival of pancreatic ductal adenocarcinoma cells. Cell Cycle. 2014;13(19):3143-9.
• [7] Clinical pipeline report, company report or official report of InxMed.
• [8] Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1.Expert Opin Ther Pat. 2017 Feb;27(2):127-143.
• [9] 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.
• [10] Structure-based discovery of cellular-active allosteric inhibitors of FAK. Bioorg Med Chem Lett. 2013 Mar 15;23(6):1779-85.
• [11] Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
• [17] c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
• [18] 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.
• [19] Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45.
• [20] Clinical pipeline report, company report or official report of BioTheryX.
• [21] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [22] CDK7 inhibitors as anticancer drugs. Cancer Metastasis Rev. 2020 Sep;39(3):805-823.
• [23] Clinical pipeline report, company report or official report of Syros Pharmaceuticals.
• [24] 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.
• [25] Preclinical metabolism and pharmacokinetics of SB1317 (TG02), a potent CDK/JAK2/FLT3 inhibitor. Drug Metab Lett. 2012 Mar;6(1):33-42.
• [26] 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.
• [27] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [28] Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666.
• [29] 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.
• [30] Evidence for irreversible inhibition of glycogen synthase kinase-3beta by tideglusib. J Biol Chem. 2012 Jan 6;287(2):893-904.
• [31] 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.
• [32] Company report (Neurim Pharmaceuticals)
• [33] 1-Azakenpaullone is a selective inhibitor of glycogen synthase kinase-3 beta. Bioorg Med Chem Lett. 2004 Jan 19;14(2):413-6.
• [34] 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.
• [35] 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.
• [36] Fragment and knowledge-based design of selective GSK-3beta inhibitors using virtual screening models. Eur J Med Chem. 2009 Jun;44(6):2361-71.
• [37] How acute promyelocytic leukaemia revived arsenic. Nat Rev Cancer. 2002 Sep;2(9):705-13.
• [38] The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IkappaB kinase. Chem Biol. 2001 Aug;8(8):759-66.
• [39] The NF B pathway: a therapeutic target in glioblastoma. Oncotarget. 2011 August; 2(8): 646-653.
• [40] Inhibition of I B phosphorylation prevents load-induced cardiac dysfunction in mice. Am J Physiol Heart Circ Physiol. 2012 Dec 15;303(12):H1435-45.
• [41] I B kinase beta inhibitor IMD-0354 suppresses airway remodelling in a Dermatophagoides pteronyssinus-sensitized mouse model of chronic asthma. Clin Exp Allergy. 2011 Jan;41(1):104-15.
• [42] Company report (Millennium)
• [43] Novel IKK inhibitors: beta-carbolines. Bioorg Med Chem Lett. 2003 Jul 21;13(14):2419-22.
• [44] UCN-01: a potent abrogator of G2 checkpoint function in cancer cells with disrupted p53. J Natl Cancer Inst. 1996 Jul 17;88(14):956-65.
• [45] Evolution of the thienopyridine class of inhibitors of IkappaB kinase-beta: part I: hit-to-lead strategies. J Med Chem. 2006 May 18;49(10):2898-908.