Table 1. PI3Kγ and PI3Kδ inhibitor pipeline. There are at least six companies developing inhibitors that are selective for phosphoinositide 3-kinase-d (PI3Kd) or selective for both PI3Kg and PI3Kd. Hematological malignancies and inflammation are the main indications being pursued. The IC50 value indicates the concentration of compound needed to inhibit PI3K signaling by 50% and serves as a rough measure of the relative selectivity of an inhibitor for one isoform over another. Lower IC50 values generally indicate greater potency.

Source: BCIQ: BioCentury Online Intelligence. Shuttleworth, S.J. et al. Curr. Med. Chem. 18, 2686-2714 (2011)

Company

Compound

Intended target(s)

Isoform selectivity
IC50 value (nM)  

Lead indication(s)

Status

Gilead Sciences Inc. (NASDAQ:GILD)

GS-1101

PI3Kd

PI3Kα: >100,000
PI3Kb: 1,820
PI3Kg: 1,240
PI3Kd: 70

Chronic lymphocytic leukemia (CLL); non-Hodgkin's lymphoma (NHL)

Phase III

Amgen Inc. (NASDAQ:AMGN)

AMG 319

PI3Kd

Not available

Hematologic malignancies

Phase I

Takeda Pharmaceutical Co. Ltd. (Tokyo:4502)/
Infinity Pharmaceuticals Inc. (NASDAQ:INFI)/
Mundipharma International Ltd.

IPI-145

PI3Kd and PI3Kg

Not available

Hematologic malignancies; autoimmune disorders

Phase I

Exelixis Inc. (NASDAQ:EXEL)/
Merck & Co. Inc. (NYSE:MRK)

XL499

PI3Kd

Not available

Allergic asthma; inflammation

Preclinical

Karus Therapeutics Ltd.

KAR4139

PI3Kd and PI3Kb

Not available

Cancer; inflammation

Preclinical

KAR4141

PI3Kd

Not available

Inflammation

Preclinical

Pathway Therapeutics Inc.

PI3Kd

PI3Kd

>=100 times more selective over PI3Ka, PI3Kb and PI3Kg

Hematologic malignancies; inflammation; respiratory disorders

Preclinical