Details of the Drug

General Information of Drug (ID: DMWU0I2)

• Drug Name: Pralsetinib
• Synonyms: GBLBJPZSROAGMF-SIYOEGHHSA-N; Blu667; 2097132-94-8; SCHEMBL18806610; SCHEMBL18789229; SCHEMBL18789228; GTPL10033; BLU-668; EX-A1944; HY-112301; CS-0044766; N-[(1S)-1-[6-(4-fluoropyrazol-1-yl)pyridin-3-yl]ethyl]-1-methoxy-4-[4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]cyclohexane-1-carboxamide

Indication

Disease Entry	ICD 11	Status	REF
Non-small-cell lung cancer	2C25.Y	Approved	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 533.6
  Topological Polar Surface Area (xlogp); 3.1
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 9
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 43900 mcgh/L [3]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 2830 mcg/L [3]
  Clearance: The apparent oral clearance of drug is 9.1 L/h [3]
  Elimination: Pralsetinib is primarily eliminated through the fecal route (73%, 66% unchanged) with a small amount found in the urine (6%, 4.8% unchanged) [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 14.7 +/- 6.5 hours [3]
  Metabolism: The drug is metabolized via the CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2 [3]
  Vd: The volume of distribution (Vd) of drug is 228 L [3]
• Chemical Identifiers:
  Formula: C27H32FN9O2
  IUPAC Name: N-[(1S)-1-[6-(4-fluoropyrazol-1-yl)pyridin-3-yl]ethyl]-1-methoxy-4-[4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]cyclohexane-1-carboxamide
  Canonical SMILES: CC1=CC(=NN1)NC2=NC(=NC(=C2)C)C3CCC(CC3)(C(=O)N[C@@H](C)C4=CN=C(C=C4)N5C=C(C=N5)F)OC
  InChI: InChI=1S/C27H32FN9O2/c1-16-11-22(33-23-12-17(2)35-36-23)34-25(31-16)19-7-9-27(39-4,10-8-19)26(38)32-18(3)20-5-6-24(29-13-20)37-15-21(28)14-30-37/h5-6,11-15,18-19H,7-10H2,1-4H3,(H,32,38)(H2,31,33,34,35,36)/t18-,19?,27?/m0/s1
  InChIKey: GBLBJPZSROAGMF-SIYOEGHHSA-N
• Cross-matching ID:
  PubChem CID: 129073603
  CAS Number: 2097132-94-8
  DrugBank ID: DB15822
  TTD ID: D0OD2I
  ACDINA ID: D01355

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Proto-oncogene c-Ret (RET)	TT4DXQT	RET_HUMAN	Inhibitor	[1]

Molecular Expression Atlas of This Drug

• The Studied Disease: Non-small-cell lung cancer
• ICD Disease Classification: 2C25.Y

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Proto-oncogene c-Ret (RET)	DTT	RET	9.18E-01	-0.36	-0.48

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Isopropyl alcohol	E00070	3776	Antimicrobial preservative; Solvent
Kyselina citronova	E00014	311	Acidulant; Antioxidant; Buffering agent; Complexing agent; Flavoring agent
Food blue 1 aluminum lake	E00512	11979396	Colorant
Ammonia	E00007	222	Alkalizing agent
Butyl alcohol	E00011	263	Flavoring agent; Solvent
Ethanol	E00023	702	Antimicrobial preservative; Penetration agent; Solvent
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Potassium hydroxide	E00233	14797	Alkalizing agent
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Sodium bicarbonate	E00424	516892	Alkalizing agent; Diluent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Water	E00035	962	Solvent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
Pregelatinized starch	E00674	Not Available	Binding agent; Diluent; Disintegrant
Shellac	E00695	Not Available	Coating agent; Film/membrane-forming agent; Microencapsulating agent; Modified-release agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Pralsetinib 100 mg capsule	100 mg	Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] FDA Approved Drug Products: GAVRETO (pralsetinib) oral capsules
• [4] 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.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [6] 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.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [8] 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. (Target id: 2185).
• [9] Clinical pipeline report, company report or official report of Turning Point Therapeutics.
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] National Cancer Institute Drug Dictionary (drug name Zeteletinib).