Details of the Drug

General Information of Drug (ID: DM3U7SZ)

Drug Name
Romiplostim
Indication
Disease Entry ICD 11 Status REF
Thrombocytopenia 3B64 Approved [1]
Multiple myeloma 2A83 Phase 2 [2]
Myelodysplastic syndrome 2A37 Phase 2 [1]
Drug Type
Small molecular drug
Sequence
>Thrombopoietin receptor binding domain amino acid sequence
IEGPTLRQWLAARA
>Amino acid sequence for Fc fusion compound
MDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYV
DGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKA
KGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD
SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKGGGGGIEGPTLR
QWLAARAGGGGGGGGIEGPTLRQWLAARA
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 238.28
Logarithm of the Partition Coefficient (xlogp) 2.5
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 1
Chemical Identifiers
Formula
C15H14N2O
IUPAC Name
(3Z)-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one
Canonical SMILES
CC1=CC(=C(N1)/C=C\\2/C3=CC=CC=C3NC2=O)C
InChI
InChI=1S/C15H14N2O/c1-9-7-10(2)16-14(9)8-12-11-5-3-4-6-13(11)17-15(12)18/h3-8,16H,1-2H3,(H,17,18)/b12-8-
InChIKey
WUWDLXZGHZSWQZ-WQLSENKSSA-N
Cross-matching ID
PubChem CID
5329098
ChEBI ID
CHEBI:91083
CAS Number
194413-58-6
DrugBank ID
DB05332
TTD ID
D01PZD
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Aryl hydrocarbon receptor (AHR) TT037IE AHR_HUMAN Modulator [3]
Fibroblast growth factor receptor 1 (FGFR1) TTRLW2X FGFR1_HUMAN Inhibitor [4]
Platelet-derived growth factor receptor alpha (PDGFRA) TT8FYO9 PGFRA_HUMAN Inhibitor [5]
Platelet-derived growth factor receptor beta (PDGFRB) TTI7421 PGFRB_HUMAN Inhibitor [5]
Proto-oncogene c-Ret (RET) TT4DXQT RET_HUMAN Inhibitor [6]
Thrombopoietin receptor (MPL) TTIHYA4 TPOR_HUMAN Modulator [7]
Tyrosine-protein kinase Kit (KIT) TTX41N9 KIT_HUMAN Inhibitor [8]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Inhibitor [4]
VEGFR1 messenger RNA (VEGFR1 mRNA) TT1VAUK VGFR1_HUMAN Inhibitor [8]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Gene/Protein Processing [9]
Cytochrome P450 1A2 (CYP1A2) OTLLBX48 CP1A2_HUMAN Gene/Protein Processing [9]
Gasdermin-D (GSDMD) OTH39BKI GSDMD_HUMAN Gene/Protein Processing [10]
High mobility group protein B1 (HMGB1) OT4B7CPF HMGB1_HUMAN Gene/Protein Processing [10]
Hypoxia-inducible factor 1-alpha (HIF1A) OTADSC03 HIF1A_HUMAN Gene/Protein Processing [11]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Protein Interaction/Cellular Processes [10]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Gene/Protein Processing [12]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Gene/Protein Processing [11]
Receptor-type tyrosine-protein kinase FLT3 (FLT3) OTMSRYMK FLT3_HUMAN Gene/Protein Processing [13]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Gene/Protein Processing [11]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Thrombocytopenia
ICD Disease Classification 3B64
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Tyrosine-protein kinase Kit (KIT) DTT KIT 2.06E-01 -0.1 -0.14
Vascular endothelial growth factor receptor 2 (KDR) DTT KDR 1.98E-01 0.11 0.2
Fibroblast growth factor receptor 1 (FGFR1) DTT FGFR1 4.79E-02 -0.03 -0.15
Platelet-derived growth factor receptor beta (PDGFRB) DTT PDGFRB 5.35E-10 0.36 0.89
VEGFR1 messenger RNA (VEGFR1 mRNA) DTT FLT1 1.64E-05 0.29 0.51
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Romiplostim (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Carfilzomib DM48K0X Major Additive thrombogenic effects by the combination of Romiplostim and Carfilzomib. Multiple myeloma [2A83] [14]

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: 6974).
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: 5056).
3 A Phase I study of the angiogenesis inhibitor SU5416 (semaxanib) in solid tumours, incorporating dynamic contrast MR pharmacodynamic end points. Br J Cancer. 2005 Oct 17;93(8):876-83.
4 Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
5 Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel... J Med Chem. 2003 Mar 27;46(7):1116-9.
6 Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors. Bioorg Med Chem. 2010 Feb 15;18(4):1482-96.
7 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
8 New anilinophthalazines as potent and orally well absorbed inhibitors of the VEGF receptor tyrosine kinases useful as antagonists of tumor-driven a... J Med Chem. 2000 Jun 15;43(12):2310-23.
9 TSU-16, (Z)-3-[(2,4-dimethylpyrrol-5-yl)methylidenyl]-2-indolinone, is a potent activator of aryl hydrocarbon receptor and increases CYP1A1 and CYP1A2 expression in human hepatocytes. Chem Biol Interact. 2010 Apr 15;185(1):33-41.
10 Activation of inflammasomes by tyrosine kinase inhibitors of vascular endothelial growth factor receptor: Implications for VEGFR TKIs-induced immune related adverse events. Toxicol In Vitro. 2021 Mar;71:105063. doi: 10.1016/j.tiv.2020.105063. Epub 2020 Dec 1.
11 SU5416 inhibited VEGF and HIF-1alpha expression through the PI3K/AKT/p70S6K1 signaling pathway. Biochem Biophys Res Commun. 2004 Nov 12;324(2):471-80. doi: 10.1016/j.bbrc.2004.09.082.
12 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
13 SU5416, a small molecule tyrosine kinase receptor inhibitor, has biologic activity in patients with refractory acute myeloid leukemia or myelodysplastic syndromes. Blood. 2003 Aug 1;102(3):795-801. doi: 10.1182/blood-2002-10-3023. Epub 2003 Mar 20.
14 Cerner Multum, Inc. "Australian Product Information.".