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Details

Stereochemistry ACHIRAL
Molecular Formula C14H8O4
Molecular Weight 240.2109
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NAPABUCASIN

SMILES

CC(=O)C1=CC2=C(O1)C(=O)C3=CC=CC=C3C2=O

InChI

InChIKey=DPHUWDIXHNQOSY-UHFFFAOYSA-N
InChI=1S/C14H8O4/c1-7(15)11-6-10-12(16)8-4-2-3-5-9(8)13(17)14(10)18-11/h2-6H,1H3

HIDE SMILES / InChI

Description

Napabucasin (BBI608) is an orally administered small molecule that blocks stem cell activity in cancer cells by targeting the signal transducer and activator of transcription 3 pathway, which is over-activated in many types of cancer and has been shown to be an important pathway in cancer stem cell-mediated propagation of cancer. Napabucasin has already shown promising efficacy on different cancer types, both as a monotherapy and in combination with conventional chemotherapeutic agents. Early-phase trials have shown promising anti-tumor efficacy when patients are treated with napabucasin in combination with standard chemotherapy agents, and preclinical results suggest that napabucasin can synergize with chemotherapy agents, such as paclitaxel, to potentially overcome drug resistance. Encouraging phase Ib/II trial results warrant further clinical study with napabucasin and paclitaxel combination therapy, especially in malignancies where there is an urgent and unmet need for effective therapeutics, such as in patients with advanced pancreatic adenocarcinoma.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
Napabucasin will be administered in continuous 28-day cycles. The starting dose of napabucasin is 240 mg twice daily (480 mg total daily dose) with approximately 12 hours between each dose. Napabucasin should be taken with fluids either 1 hour prior to a meal or 2 hours after a meal.
Route of Administration: Oral
In Vitro Use Guide
Colo205, Dld1, Hct116, RKO, SW480, AGS, MKN-28, MKN-45, 786-0, ACHN, Huh7, Panc1, Du145, HeLa, PC3, and A431 cells were plated under cancer stem cell culture conditions on coated 96-well plates. After 72 h of culture, wells were dosed with the indicated compounds (Napabucasin). Seventy-two hours or 24 h after dosing, CellTiter-Glo 2.0 was added to each well, and the luminescence was measured as described by the manufacturer (Promega)