Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT6L509)

• DTT Name: Coagulation factor IIa (F2)
• Synonyms: Prothrombin; Coagulation factor II
• Gene Name: F2
• DTT Type: Successful target; [1]
• Related Disease:
  Bleeding disorder [ICD-11: GA20-GA21]
  Coagulation defect [ICD-11: 3B10]
  Ischaemic/haemorrhagic stroke [ICD-11: 8B20]
  Multiple sclerosis [ICD-11: 8A40]
  Myocardial infarction [ICD-11: BA41-BA43]
  Nutritional deficiency [ICD-11: 5B50-5B71]
  Thrombocytopenia [ICD-11: 3B64]
  Thrombosis [ICD-11: DB61-GB90]
• BioChemical Class: Peptidase
• UniProt ID: THRB_HUMAN
• TTD ID: T94033
• EC Number: EC 3.4.21.5
• Sequence:
  MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLEREC
  VEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHV
  NITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQE
  CSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASA
  QAKALSKHQDFNSAVQLVENFCRNPDGDEEGVWCYVAGKPGDFGYCDLNYCEEAVEEETG
  DGLDEDSDRAIEGRTATSEYQTFFNPRTFGSGEADCGLRPLFEKKSLEDKTERELLESYI
  DGRIVEGSDAEIGMSPWQVMLFRKSPQELLCGASLISDRWVLTAAHCLLYPPWDKNFTEN
  DLLVRIGKHSRTRYERNIEKISMLEKIYIHPRYNWRENLDRDIALMKLKKPVAFSDYIHP
  VCLPDRETAASLLQAGYKGRVTGWGNLKETWTANVGKGQPSVLQVVNLPIVERPVCKDST
  RIRITDNMFCAGYKPDEGKRGDACEGDSGGPFVMKSPFNNRWYQMGIVSWGEGCDRDGKY
  GFYTHVFRLKKWIQKVIDQFGE
• Function: Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.
• KEGG Pathway:
  Neuroactive ligand-receptor interaction (hsa04080)
  Complement and coagulation cascades (hsa04610)
  Regulation of actin cytoskeleton (hsa04810)
• Reactome Pathway:
  Common Pathway of Fibrin Clot Formation (R-HSA-140875)
  Gamma-carboxylation of protein precursors (R-HSA-159740)
  Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus (R-HSA-159763)
  Removal of aminoterminal propeptides from gamma-carboxylated proteins (R-HSA-159782)
  Cell surface interactions at the vascular wall (R-HSA-202733)
  Peptide ligand-binding receptors (R-HSA-375276)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  G alpha (q) signalling events (R-HSA-416476)
  Thrombin signalling through proteinase activated receptors (PARs) (R-HSA-456926)
  Intrinsic Pathway of Fibrin Clot Formation (R-HSA-140837)

Molecular Interaction Atlas (MIA) of This DTT

11 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Anisindione	DM2C48U	Coagulation defect	3B10.0	Approved	[2]
Argatroban	DMFI46A	Thrombosis	DB61-GB90	Approved	[3], [4], [5]
ATryn antithrombin	DM79Y2T	Multiple sclerosis	8A40	Approved	[6]
Bivalirudin	DMECRX1	Thrombocytopenia	3B64	Approved	[4], [7], [8]
Dabigatran	DMDI6R4	Stroke	8B20	Approved	[9]
Desirudin Recombinant	DM2BTFN	Coagulation defect	3B10.0	Approved	[10]
Human prothrombin complex concentrate	DMPHVQ1	Bleeding disorder	GA20-GA21	Approved	[11]
Lepirudin	DM1I3D5	Thrombocytopenia	3B64	Approved	[12]
Pyridoxal Phosphate	DMO2K0J	Malnutrition	5B50-5B71	Approved	[8]
Ximelegatran	DMU8ANS	Myocardial infarction	BA41-BA43	Approved	[1]
Hirudin	DMYOC29	N. A.	N. A.	Phase 4	[13], [4], [7]

16 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Melagatran	DM4W8RE	N. A.	N. A.	Phase 3	[14]
SR-123781A	DM5WQ2U	Venous thrombosis	BA43	Phase 2/3	[15]
EFEGATRAN SULFATE HYDRATE	DMX4RSD	Myocardial infarction	BA41-BA43	Phase 2	[16]
EP-217609	DMPC4EK	Thrombosis	DB61-GB90	Phase 2	[17]
LB-30870	DM0OHX3	Myocardial infarction	BA41-BA43	Phase 2	[16]
NU-172	DMORNVB	Thrombosis	DB61-GB90	Phase 2	[18], [19]
Odiparcil	DMWCBY7	Cardiovascular disease	BA00-BE2Z	Phase 2	[20]
Pegmusirudin	DMPD3X6	Angina pectoris	BA40	Phase 2	[11]
Recombinant RGD-hirudin	DMV0A28	Thrombosis	DB61-GB90	Phase 2	[21]
TF0023	DMF61ML	Heart attack	BA41	Phase 2	[22]
AZD-8165	DM8DMI0	Thrombosis	DB61-GB90	Phase 1	[11]
DP-4088	DMXZ6A0	Coagulation defect	3B10.0	Phase 1	[11]
EP-42675	DMKR3GD	Thrombosis	DB61-GB90	Phase 1	[23]
RWJ-671818	DMJVCS1	Thrombosis	DB61-GB90	Phase 1	[24]
Solulin	DMB3WJF	Thrombosis	DB61-GB90	Phase 1	[25]
SSR-128428	DMOJA7N	Thrombosis	DB61-GB90	Phase 1	[26]

29 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ximelagatran	DMABRJL	Coagulation defect	3B10.0	Withdrawn from market	[27], [4]
AZD0837	DMA9Q2V	Nonvalvular atrial fibrillation	BC81.3Y	Discontinued in Phase 2	[28]
Dermolastin	DM6WSU2	Atopic dermatitis	EA80	Discontinued in Phase 2	[29], [30], [31], [32]
INOGATRAN	DM6HDO3	Myocardial infarction	BA41-BA43	Discontinued in Phase 2	[33]
Napsagatran	DM8L4Z0	Myocardial infarction	BA41-BA43	Discontinued in Phase 2	[34]
SSR-182289	DMN7BM3	Myocardial infarction	BA41-BA43	Discontinued in Phase 2	[16]
Vasoflux	DMHCOFM	Myocardial infarction	BA41-BA43	Discontinued in Phase 2	[35]
ARC-183	DMKLCRI	Blood forming organ disorder	JB64.1	Discontinued in Phase 1	[36]
BCX-1470	DMN2XR7	Bleeding disorder	GA20-GA21	Discontinued in Phase 1	[37]
CJC-1004	DM3Q8UW	Thrombosis	DB61-GB90	Discontinued in Phase 1	[38]
CVS-1123	DMDRFZV	Myocardial infarction	BA41-BA43	Discontinued in Phase 1	[39]
GW-473178	DMRQVI9	Heart arrhythmia	BC65	Discontinued in Phase 1	[40]
Licostinel	DMMWCU3	Neurological disorder	6B60	Discontinued in Phase 1	[41]
MPC-0920	DMMVG34	Thrombosis	DB61-GB90	Discontinued in Phase 1	[42]
S-18326	DMX59E8	Myocardial infarction	BA41-BA43	Discontinued in Phase 1	[16]
UK-156406	DMGFPIY	Myocardial infarction	BA41-BA43	Discontinued in Phase 1	[16]
BCH-2763	DM3TP8X	Thrombosis	DB61-GB90	Terminated	[43]
BMS-189664	DMV3B5Y	Myocardial infarction	BA41-BA43	Terminated	[16]
CVS-995	DMMDO3X	Myocardial infarction	BA41-BA43	Terminated	[44]
DuP 714	DMZOCHT	Thrombosis	DB61-GB90	Terminated	[45]
Efegatran	DM7ROS1	N. A.	N. A.	Terminated	[45]
GS-522	DMT6S9B	Thrombosis	DB61-GB90	Terminated	[46]
Hementin	DM5HMZW	Thrombosis	DB61-GB90	Terminated	[47]
L-373890	DMOKZ2V	Thrombosis	DB61-GB90	Terminated	[48]
L-374,087	DMK2QW0	Thrombosis	DB61-GB90	Terminated	[49]
LB30057	DMYGJCL	N. A.	N. A.	Terminated	[50]
Org-34092	DM3VWZF	Thrombosis	DB61-GB90	Terminated	[11]
PPACK	DMLY2TN	N. A.	N. A.	Terminated	[45]
SR-80027A	DM6ASLF	Thrombosis	DB61-GB90	Terminated	[51]

86 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(3,4-dichlorophenyl)(1H-pyrazol-1-yl)methanone	DMNVDLI	Discovery agent	N.A.	Investigative	[52]
(3-nitro-1H-pyrazol-1-yl)(p-tolyl)methanone	DMT9FZD	Discovery agent	N.A.	Investigative	[52]
(3-nitro-1H-pyrazol-1-yl)(phenyl)methanone	DMD4Z6H	Discovery agent	N.A.	Investigative	[52]
(4-bromo-1H-pyrazol-1-yl)(p-tolyl)methanone	DM31OSD	Discovery agent	N.A.	Investigative	[52]
(4-nitro-1H-pyrazol-1-yl)(o-tolyl)methanone	DMBPL3J	Discovery agent	N.A.	Investigative	[52]
(4-nitro-1H-pyrazol-1-yl)(phenyl)methanone	DMIDUO9	Discovery agent	N.A.	Investigative	[52]
1,2,3,4,6-penta-O-galloyl-beta-D-glucose	DMTK650	Discovery agent	N.A.	Investigative	[53]
1-(HYDROXYMETHYLENEAMINO)-8-HYDROXY-OCTANE	DMBTLIJ	Discovery agent	N.A.	Investigative	[54]
1-benzoyl-N-phenyl-1H-pyrazole-3-carboxamide	DMG5MNZ	Discovery agent	N.A.	Investigative	[52]
2-(2-Hydroxy-phenyl)-1H-indole-5-carboxamidine	DM3UMYD	Discovery agent	N.A.	Investigative	[55]
2-NAPHTHALENESULFONIC ACID	DMZ4LJ7	Discovery agent	N.A.	Investigative	[54]
2-nas-phe(3-am)-4-(2-guanidinoethyl)piperidine	DMFXKN1	Discovery agent	N.A.	Investigative	[56]
3-chlorophenyl 2-oxo-2H-chromene-3-carboxylate	DMZ0F7E	Discovery agent	N.A.	Investigative	[57]
4-(2,5-DIAMINO-5-HYDROXY-PENTYL)-PHENOL	DM3D8OK	Discovery agent	N.A.	Investigative	[54]
4-(3,4-Diethoxy-benzylamino)-benzamidine	DMIZXYM	Discovery agent	N.A.	Investigative	[58]
4-(4-Benzyloxy-3-methoxy-benzylamino)-benzamidine	DME3PUT	Discovery agent	N.A.	Investigative	[58]
4-hydroxyphenylpyruvic acid	DM0564K	Discovery agent	N.A.	Investigative	[54]
4-iodobenzo[b]thiophene 2-carboxamidine	DMXAEGF	N. A.	N. A.	Investigative	[54]
4-TERT-BUTYLBENZENESULFONIC ACID	DMGCYS1	Discovery agent	N.A.	Investigative	[54]
4-[3-(4-CHLOROPHENYL)-1H-PYRAZOL-5-YL]PIPERIDINE	DMJI6AM	Discovery agent	N.A.	Investigative	[54]
5-desgalloylstachyurin	DM6TM1L	Discovery agent	N.A.	Investigative	[53]
6-(2-HYDROXY-CYCLOPENTYL)-7-OXO-HEPTANAMIDINE	DMA2CPG	Discovery agent	N.A.	Investigative	[54]
AC-(D)PHE-PRO-BOROHOMOLYS-OH	DMZ0RP5	Discovery agent	N.A.	Investigative	[54]
AC-(D)PHE-PRO-BOROHOMOORNITHINE-OH	DMPHV7K	Discovery agent	N.A.	Investigative	[54]
AC-(D)PHE-PRO-BOROLYS-OH	DM2YWRL	Discovery agent	N.A.	Investigative	[54]
Bbs-Arg-(D-Pip)-Gly-(EQKLISEEDL)-Gly-Hir	DMMJ4I5	Discovery agent	N.A.	Investigative	[59]
Bbs-Arg-(D-Pip)-Gly-(SPH(pY)EKVS)-Gly-Hir	DM8TH4B	Discovery agent	N.A.	Investigative	[59]
Bbs-Arg-(D-Pip)-Gly-(SPHYEKVS)-Gly-Hir	DMQVRHG	Discovery agent	N.A.	Investigative	[59]
Bbs-Arg-(D-Pip)-Gly-S-(GS)1-Gly-Hir	DMTU0HR	Discovery agent	N.A.	Investigative	[59]
Bbs-Arg-(D-Pip)-Gly-S-(GS)11-Gly-Hir	DMXECFJ	Discovery agent	N.A.	Investigative	[59]
Bbs-Arg-(D-Pip)-Gly-S-(GS)13-Gly-Hir	DM5N6YE	Discovery agent	N.A.	Investigative	[59]
Bbs-Arg-(D-Pip)-Gly-S-(GS)3-Gly-Hir	DMEL2GK	Discovery agent	N.A.	Investigative	[59]
Bbs-Arg-(D-Pip)-Gly-S-(GS)5-Gly-Hir	DMCN48J	Discovery agent	N.A.	Investigative	[59]
Bbs-Arg-(D-Pip)-Gly-S-(GS)7-Gly-Hir	DMLK5I0	Discovery agent	N.A.	Investigative	[59]
Bbs-Arg-(D-Pip)-Gly-S-(GS)9-Gly-Hir	DMLZ5R6	Discovery agent	N.A.	Investigative	[59]
BENZOTHIAZOLE	DMV7MPL	Discovery agent	N.A.	Investigative	[54]
Beta-(2-Naphthyl)-Alanine	DMP21ZO	Discovery agent	N.A.	Investigative	[54]
Beta-phenyl-D-phenylalanyl-N-propyl-L-prolinamide	DMQXMKB	Discovery agent	N.A.	Investigative	[54]
BMS-344577	DM9WRUG	Discovery agent	N.A.	Investigative	[60]
BMS-740808	DMQ24TI	Discovery agent	N.A.	Investigative	[61]
bufrudin	DMWQ3RH	Discovery agent	N.A.	Investigative	[62], [63]
CASUARIIN	DM5E21C	Discovery agent	N.A.	Investigative	[53]
CHLORODYSINOSIN A	DMGS3FI	Discovery agent	N.A.	Investigative	[64]
COCHINCHINENENE B	DMCSAIJ	Discovery agent	N.A.	Investigative	[65]
COCHINCHINENIN B	DMIGB7N	Discovery agent	N.A.	Investigative	[65]
CRA_8696	DM3IZOP	Discovery agent	N.A.	Investigative	[54]
CVS-1578	DMO9UMK	Discovery agent	N.A.	Investigative	[66], [67]
Cyclotheonamide E	DM8HG0K	Discovery agent	N.A.	Investigative	[68]
Cyclotheonamide E4	DM2E5VZ	Discovery agent	N.A.	Investigative	[68]
Cyclotheonamide E5	DMCA76M	Discovery agent	N.A.	Investigative	[68]
D-leucyl-N-(3-chlorobenzyl)-L-prolinamide	DMVN93B	Discovery agent	N.A.	Investigative	[54]
D-leucyl-N-(4-carbamimidoylbenzyl)-L-prolinamide	DMIFCHL	Discovery agent	N.A.	Investigative	[54]
D-phenylalanyl-N-(3-chlorobenzyl)-L-prolinamide	DMGD7JM	Discovery agent	N.A.	Investigative	[54]
D-phenylalanyl-N-(3-fluorobenzyl)-L-prolinamide	DM5XHA6	Discovery agent	N.A.	Investigative	[54]
D-phenylalanyl-N-(3-methylbenzyl)-L-prolinamide	DMV9RAN	Discovery agent	N.A.	Investigative	[54]
D-phenylalanyl-N-benzyl-L-prolinamide	DMHNR63	Discovery agent	N.A.	Investigative	[54]
D-Pro-Phe-Arg chloromethyl ketone	DMRJQ8X	Discovery agent	N.A.	Investigative	[69]
Desirudine	DMB07WE	Discovery agent	N.A.	Investigative	[8]
DYSINOSIN A	DMU42C1	Discovery agent	N.A.	Investigative	[64]
Enoxaprin	DMYJ8ZB	Discovery agent	N.A.	Investigative	[70]
Gamma-Carboxy-Glutamic Acid	DMZMCT0	Discovery agent	N.A.	Investigative	[71]
GR-133686	DMQH8PK	Discovery agent	N.A.	Investigative	[72]
Haempatch	DMO6MGJ	Bleeding disorder	GA20-GA21	Investigative	[11]
Hemi-Babim	DMXP276	Discovery agent	N.A.	Investigative	[54]
Heparin-Cantithrombin III	DM7U491	Discovery agent	N.A.	Investigative	[73]
L-370,518	DMC1Z0L	Discovery agent	N.A.	Investigative	[7]
L-375378	DMQWKPM	Discovery agent	N.A.	Investigative	[74]
LB30812	DM3H9ZY	Discovery agent	N.A.	Investigative	[75]
Lysophosphotidylserine	DMIG3FX	Discovery agent	N.A.	Investigative	[71]
Macrocyclic tripeptide motif	DMFULZO	Discovery agent	N.A.	Investigative	[76]
Melogatran	DME54M7	Discovery agent	N.A.	Investigative	[73]
Methyl L-phenylalaninate	DMBHUKV	Discovery agent	N.A.	Investigative	[54]
METHYL-PHE-PRO-AMINO-CYCLOHEXYLGLYCINE	DMR7HV3	Discovery agent	N.A.	Investigative	[54]
N4-(N,N-diphenylcarbamoyl)-aminoguanidine	DMYPZMO	Discovery agent	N.A.	Investigative	[54]
OSCILLARIN	DMK6X5P	Discovery agent	N.A.	Investigative	[64]
Pedunculagin	DMKLRCX	Discovery agent	N.A.	Investigative	[53]
RAZAXABAN	DMPML15	Discovery agent	N.A.	Investigative	[77]
RWJ-50353	DMRPYGX	Discovery agent	N.A.	Investigative	[78]
S-2238	DM3GS2X	Discovery agent	N.A.	Investigative	[79]
SC-79407	DMD71VB	Discovery agent	N.A.	Investigative	[49]
TB-101	DMCZIFS	Bleeding disorder	GA20-GA21	Investigative	[11]
TB-102	DMUN8CG	Bleeding disorder	GA20-GA21	Investigative	[11]
Tellimagrandin II	DM60HU5	Discovery agent	N.A.	Investigative	[53]
Tumor vascular thrombogen	DMIRQ65	Solid tumour/cancer	2A00-2F9Z	Investigative	[11]
VE-04051645	DM3GADP	Solid tumour/cancer	2A00-2F9Z	Investigative	[11]
Vitamin K	DMN6EZY	Discovery agent	N.A.	Investigative	[80]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Thrombocytopenia	3B64	Whole blood	7.64E-01	0.2	0.77
Atopic dermatitis	EA90	Skin	7.71E-01	0.02	0.22

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