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]
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Affected Organisms

Humans and other mammals

ATC Code

B02BX04: Romiplostim

B02BX: Other systemic hemostatics

B02B: VITAMIN K AND OTHER HEMOSTATICS

B02: ANTIHEMORRHAGICS

B: BLOOD AND BLOOD FORMING ORGANS

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
UNII: GN5XU2DXKV
DrugBank ID: DB05332
TTD ID: D01PZD

Repurposed Drugs (RPD)

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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]

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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]

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Molecular Interaction Atlas (MIA)

MIA Detail

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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)

MEA Detail

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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]
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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.".