Details of the Drug

General Information of Drug (ID: DM5PFIJ)

Drug Name

Givosiran

Synonyms

1639325-43-1; N-[1,3-Bis[3-[3-[5-[(2R,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypentanoylamino]propylamino]-3-oxopropoxy]-2-[[3-[3-[5-[(2R,3R,4R,5R,6R)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypentanoylamino]propylamino]-3-oxopropoxy]methyl]propan-2-yl]-12-[(2R,4R)-4-hydroxy-2-methylpyrrolidin-1-yl]-12-oxododecanamide; Fitusiran; Givlaari; Givosiran [INN]; Givosiran [USAN]; Givosiran [USAN:INN]; ALN-AS1; UNII-ROV204583W; ROV204583W; WHO 10280

Indication

Disease Entry	ICD 11	Status	REF
Acute intermittent hepatic porphyria	5C58.11	Approved	[1]

Drug Type

Small interfering RNA

Sequence

>Subunit 1
CAGAAAGAGUGUCUCAUCUUA
>Subunit 2
UAAGAUGAGACACUCUUUCUGGU

Structure

3D MOL is unavailable

2D MOL

#Ro5 Violations (Lipinski): 5

Molecular Weight (mw)

1711

Topological Polar Surface Area (xlogp)

-5.9

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 4130 mcgh/L [2]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 321 mcg/L [2]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 3 h [2]
Clearance: The clearance of drug is 35.1 L/h [2]
Elimination: Approximately 5-14% of the dose recovered in urine is unchanged parent drug [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 6 hours [2]
Metabolism: The drug is metabolized via nuclease enzymes [2]
Vd: The volume of distribution (Vd) of drug is 10.4 L [2]

Chemical Identifiers

Formula: C78H139N11O30
IUPAC Name: N-[1,3-bis[3-[3-[5-[3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypentanoylamino]propylamino]-3-oxopropoxy]-2-[[3-[3-[5-[3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxypentanoylamino]propylamino]-3-oxopropoxy]methyl]propan-2-yl]-12-(4-hydroxy-2-methylpyrrolidin-1-yl)-12-oxododecanamide
Canonical SMILES: CC1CC(CN1C(=O)CCCCCCCCCCC(=O)NC(COCCC(=O)NCCCNC(=O)CCCCOC2C(C(C(C(O2)CO)O)O)NC(=O)C)(COCCC(=O)NCCCNC(=O)CCCCOC3C(C(C(C(O3)CO)O)O)NC(=O)C)COCCC(=O)NCCCNC(=O)CCCCOC4C(C(C(C(O4)CO)O)O)NC(=O)C)O
InChI: InChI=1S/C78H139N11O30/c1-50-42-54(96)43-89(50)65(104)26-12-10-8-6-5-7-9-11-25-64(103)88-78(47-111-39-27-61(100)82-33-19-30-79-58(97)22-13-16-36-114-75-66(85-51(2)93)72(108)69(105)55(44-90)117-75,48-112-40-28-62(101)83-34-20-31-80-59(98)23-14-17-37-115-76-67(86-52(3)94)73(109)70(106)56(45-91)118-76)49-113-41-29-63(102)84-35-21-32-81-60(99)24-15-18-38-116-77-68(87-53(4)95)74(110)71(107)57(46-92)119-77/h50,54-57,66-77,90-92,96,105-110H,5-49H2,1-4H3,(H,79,97)(H,80,98)(H,81,99)(H,82,100)(H,83,101)(H,84,102)(H,85,93)(H,86,94)(H,87,95)(H,88,103)
InChIKey: RUPXJRIDSUCQAN-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 156323004
CAS Number: 1639325-43-1
DrugBank ID: DB15066
TTD ID: DF36DY
ACDINA ID: D01125

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
ALAS1 messenger RNA (ALAS1 mRNA)	TTG1FXO	HEM1_HUMAN	Inhibitor	[1]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

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

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Water	E00035	962	Solvent
--------------------

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Givosiran 189 mg/ml Injection	189 mg/ml	Injection	Subcutaneous

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. 2019
2	FDA Approved Drug Products: Givlaari subcutaneous injection