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
Logarithm of the Partition Coefficient (xlogp) -5.9
Rotatable Bond Count (rotbonds) 63
Hydrogen Bond Donor Count (hbonddonor) 20
Hydrogen Bond Acceptor Count (hbondacc) 30
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-[(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
Canonical SMILES
C[C@@H]1C[C@H](CN1C(=O)CCCCCCCCCCC(=O)NC(COCCC(=O)NCCCNC(=O)CCCCO[C@H]2[C@@H]([C@H]([C@H]([C@H](O2)CO)O)O)NC(=O)C)(COCCC(=O)NCCCNC(=O)CCCCO[C@H]3[C@@H]([C@H]([C@H]([C@H](O3)CO)O)O)NC(=O)C)COCCC(=O)NCCCNC(=O)CCCCO[C@H]4[C@@H]([C@H]([C@H]([C@H](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)/t50-,54-,55-,56-,57-,66-,67-,68-,69+,70+,71+,72-,73-,74-,75-,76-,77-/m1/s1
InChIKey
RUPXJRIDSUCQAN-PQNNUJSWSA-N
Cross-matching ID
PubChem CID
119058042
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) 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