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Details

Stereochemistry ABSOLUTE
Molecular Formula C42H56F2N8O6
Molecular Weight 806.9408
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BIRINAPANT

SMILES

CC[C@H](NC(=O)[C@H](C)NC)C(=O)N1C[C@@H](O)C[C@H]1CC2=C(NC3=CC(F)=CC=C23)C4=C(C[C@@H]5C[C@H](O)CN5C(=O)[C@H](CC)NC(=O)[C@H](C)NC)C6=CC=C(F)C=C6N4

InChI

InChIKey=PKWRMUKBEYJEIX-DXXQBUJASA-N
InChI=1S/C42H56F2N8O6/c1-7-33(49-39(55)21(3)45-5)41(57)51-19-27(53)15-25(51)17-31-29-11-9-23(43)13-35(29)47-37(31)38-32(30-12-10-24(44)14-36(30)48-38)18-26-16-28(54)20-52(26)42(58)34(8-2)50-40(56)22(4)46-6/h9-14,21-22,25-28,33-34,45-48,53-54H,7-8,15-20H2,1-6H3,(H,49,55)(H,50,56)/t21-,22-,25-,26-,27-,28-,33-,34-/m0/s1

HIDE SMILES / InChI

Molecular Formula C42H56F2N8O6
Molecular Weight 806.9408
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 8 / 8
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT01681368 | https://clinicaltrials.gov/ct2/show/NCT01486784 | https://clinicaltrials.gov/ct2/show/NCT02756130 | https://www.ncbi.nlm.nih.gov/pubmed/28337955

Birinapant is a parenterally administered bivalent peptidomimetic of the SMAC protein (Second Mitochondria-derived Activator of Caspases) and is therefore known as a SMAC mimetic compound. Birinapant is a particularly potent antagonist of two members of the Inhibitor of Apoptosis Proteins (IAP) family, cIAP-1, and cIAP-2. cIAP-1 and -2 are ubiquitin ligases whose expression can protect cells from apoptosis and cause pro-survival effects of TNF-α and related ligands. When Birinapant binds to cIAP-1 or -2 it causes the protein to ubiquitinate itself, which in turn drives the degradation of the protein. In this way, birinapant suppresses the levels of cIAP-1 and cIAP-2 and therefore switches cell signaling to drive tumor cell apoptosis in the presence of TNF-α. Birinapant has been shown to give rise to sustained and substantial reductions of cIAP1 levels in Peripheral Blood Mononuclear Cells (PBMCs) and tumor tissue. To date, Birinapant has been dosed in approximately 450 patients across 9 studies. The majority of studies was in oncology (one in HBV) and primarily recruited patients with refractory solid tumors & hematological malignancies (dominated by ovarian, colorectal, acute myeloid leukemia and Myelodysplastic syndromes). Overall Birinapant has shown acceptable safety and tolerability for further development in oncology indications. The current plans are to study Birinapant clinically in combination with Keytruda® for the treatment solid tumors and in an Investigator-Initiated study at UCLA for high-grade serous carcinoma (HGSC) in combination with platinum-based chemotherapy.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
The novel SMAC mimetic birinapant exhibits potent activity against human melanoma cells.
2013 Apr 1
Smac mimetic Birinapant induces apoptosis and enhances TRAIL potency in inflammatory breast cancer cells in an IAP-dependent and TNF-α-independent mechanism.
2013 Jan
Birinapant (TL32711), a bivalent SMAC mimetic, targets TRAF2-associated cIAPs, abrogates TNF-induced NF-κB activation, and is active in patient-derived xenograft models.
2014 Apr
Molecular pathways: targeting inhibitor of apoptosis proteins in cancer--from molecular mechanism to therapeutic application.
2014 Jan 15
Patents

Patents

Sample Use Guides

47mg/m^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
Route of Administration: Intravenous
Twelve melanoma cell lines (WM115, Sk-Mel-1, Sk-Mel-5, Malme-3M, MeWo, Sk-Mel-2, WM35, WM3211, WM1366, WM1719C, WM3060 and DSMZ) were used for activity evaluation. Cells were seeded in 96-well plates and treated with birinapant (Active Biochem, NJ, USA) and dacarbazine (Medac GmbH, Germany) using 5x5 concentration-combination matrices, with the concentrations for birinapant ranging from 1 nM to 1 μM and for dacarbazine ranging from 1 μg/ml to 1 mg/ml. Drugs were applied simultaneously. Cells were treated for 24 h or 48 h and subsequently stained with propidium iodide (1.3 μg/ml for 10 min) for cell death measurements.
Substance Class Chemical
Created
by admin
on Fri Dec 15 17:57:43 GMT 2023
Edited
by admin
on Fri Dec 15 17:57:43 GMT 2023
Record UNII
6O4Z07B57R
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BIRINAPANT
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
BIRINAPANT [USAN]
Common Name English
PROPANAMIDE, N,N'-((6,6'-DIFLUORO(2,2'-BI-1H-INDOLE)-3,3'-DIYL)BIS(METHYLENE((2R,4S)-4-HYDROXY-2,1-PYRROLIDINEDIYL)((1S)-1-ETHYL-2-OXO-2,1-ETHANEDIYL)))BIS(2-(METHYLAMINO)-, (2S,2'S)-
Systematic Name English
birinapant [INN]
Common Name English
TL32711
Code English
TL-32711
Code English
N,N'-((6,6'-DIFLUORO(1H,1'H-2,2'-BIINDOLE)- 3,3'-DIYL)BIS(METHYLENE((2R,4S)-4-HYDROXYPYRROLIDINE-2,1-DIYL)((2S)-1- OXOBUTANE-1,2-DIYL) BIS((2S)-2-(METHYLAMINO)PROPANAMIDE)
Common Name English
Birinapant [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C274
Created by admin on Fri Dec 15 17:57:43 GMT 2023 , Edited by admin on Fri Dec 15 17:57:43 GMT 2023
Code System Code Type Description
ChEMBL
CHEMBL3039522
Created by admin on Fri Dec 15 17:57:43 GMT 2023 , Edited by admin on Fri Dec 15 17:57:43 GMT 2023
PRIMARY
USAN
YY-132
Created by admin on Fri Dec 15 17:57:43 GMT 2023 , Edited by admin on Fri Dec 15 17:57:43 GMT 2023
PRIMARY
DRUG BANK
DB11782
Created by admin on Fri Dec 15 17:57:43 GMT 2023 , Edited by admin on Fri Dec 15 17:57:43 GMT 2023
PRIMARY
PUBCHEM
49836020
Created by admin on Fri Dec 15 17:57:43 GMT 2023 , Edited by admin on Fri Dec 15 17:57:43 GMT 2023
PRIMARY
EPA CompTox
DTXSID30155057
Created by admin on Fri Dec 15 17:57:43 GMT 2023 , Edited by admin on Fri Dec 15 17:57:43 GMT 2023
PRIMARY
FDA UNII
6O4Z07B57R
Created by admin on Fri Dec 15 17:57:43 GMT 2023 , Edited by admin on Fri Dec 15 17:57:43 GMT 2023
PRIMARY
SMS_ID
100000156891
Created by admin on Fri Dec 15 17:57:43 GMT 2023 , Edited by admin on Fri Dec 15 17:57:43 GMT 2023
PRIMARY
EVMPD
SUB130963
Created by admin on Fri Dec 15 17:57:43 GMT 2023 , Edited by admin on Fri Dec 15 17:57:43 GMT 2023
PRIMARY
CAS
1260251-31-7
Created by admin on Fri Dec 15 17:57:43 GMT 2023 , Edited by admin on Fri Dec 15 17:57:43 GMT 2023
PRIMARY
INN
9587
Created by admin on Fri Dec 15 17:57:43 GMT 2023 , Edited by admin on Fri Dec 15 17:57:43 GMT 2023
PRIMARY
NCI_THESAURUS
C88295
Created by admin on Fri Dec 15 17:57:43 GMT 2023 , Edited by admin on Fri Dec 15 17:57:43 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
TARGET -> INHIBITOR
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY