Table 2 Inhibitors of the PI3K/AKT/mTOR pathway in the clinic

Afuresertib (GSK2110183)

AKT 1/2/3

Oral

ATP competitive

I, II

MM, CLL, Solid cancers

BAY1125976

AKT 1/2

Oral

Allosteric, Non-ATP competitive

I

Advanced solid tumors

RX-0201 (Archexin)

AKT 1

IV

Antisense oligodeoxymucleotide

I/II, II

Pancreatic, Renal

ARQ 092

Pan AKT, selectivity for AKT1

Oral

ATP competitive

I

Solid tumors, recurrent Lymphoma

GDC-0068

AKT 1/2/3

Oral

Non-ATP competitive

I, II

Solid cancers

Uprosertib (GSK2141795)

AKT 1/2/3

Oral

ATP competitive

II

Solid cancers, AML, MM

MK2206

Pan AKT, selectivity for AKT1

Oral

Allosteric, Non-ATP competitive

II

Solid tumors, lymphoma

SR13668

AKT

Oral

Blocks AKT phosphorylation

I

Healthy volunteers (completed)

LY2780301

AKT/p70S6K

Oral

ATP competitive

I/II

Advanced solid tumors, non-hogdkin’s lymphoma

AZD5363

AKT, 1/2/3 P70S6K/PKA

Oral

ATP competitive

I/II

Solid cancers

ONC201 (TIC10)

AKT/ERK

Oral

Indirect

I/II

Advanced solid tumors

BKM120 (buparlisib)

PI3K

Oral

ATP competitive

II, III

Advanced cancers

ZSTK474

PI3K

Oral

S-triazine derivative, ATP-competitive

I/II

Advanced solid tumors

Copanlisib (BAY 80–6946)

PI3K

IV

Imidazolinoquinazoline derivative

I. II

Advanced solid tumors, NHL

PX-866

PI3K

Oral

Wortmannin analogue, irreversibly binds catalytic site

I/II

Solid tumors

XL147 (SAR245408)

PI3K (MEK/ERK)

Oral

ATP competitive

I

Advanced solid tumors

BYL719

PI3K alpha

Oral

2-aminothiazole derivative

I/II

Advanced solid tumors

INK1117 (MLN1117)

PI3K alpha

Oral

I

Metastatic solid tumors

AZD8186

PI3K beta

Oral

I

CRPC, sqNSCLC, TNBC, PTEN deficient advanced cancers

GSK2636771

PI3K beta

Oral

substituted benzimidazole

I/II

CRPC, PTEN deficient solid tumors

Idelalisib (Zydelig, CAL-101, GS-1101)

PI3K delta

Oral

Quinazoline class

III

NHL, FDA approved for relapsed CLL, SLL, FL

INCB040093

PI3K delta

Oral

I

B cell malignancies

INCB050465

PI3K delta

I

Relaposed/ refractory B cell malignancies

BAY1082439

PI3K alpha/beta

Oral

I

Advanced solid tumors

GDC-0941 bismesylate

PI3K alpha/delta

Oral

ATP competitive

I/II

TNBC, NSCLC

AZD8835

PI3K alpha/delta

Oral

I

Advanced solid tumors

GS-9820 (CAL-120)

PI3K beta/delta

Oral

Ib

Lymphoid malignancies

RP6530

PI3K gamma/delta

Oral

I

Hematological malignancies

IPI-145

PI3K gamma/delta

Oral

ATP competitive

I, III

Hematological malignancies, follicular lymphoma

DCBCI0901

PI3K/mTORC1/2

IV

I

Advanced solid tumors

P7170

PI3K/mTOR/DNA-PK/ALK-1

Oral

I

Advanced refractory tumors

VS-5584

PI3K/mTOR

Oral

I

Non hematological cancers, metastatic cancers, Lymphoma

DS-7423

PI3K/mTOR

Oral

I

Solid tumors, completed

PF-05212384

PI3K/mTOR

IV

I

Advanced solid tumors

BEZ235

PI3K/mTOR

Oral

Imidazo (4,5) quinoline derivative, ATP competitive

I/II

Advanced solid tumors

XL765 (SAR245409)

PI3K/mTOR

Oral

I/II

Advanced solid tumors

BGT226

PI3K/mTOR

Oral

I/II

Advanced solid cancers, completed

GDC-0980

PI3K/mTOR

I/II

NHL, EC, Solid tumors

GSK2126458

PI3K/mTOR

Oral

Pyridylsulfonamide derivative

I

Refractory solid tumors

PWT33597 mesylate (VCD-597)

PI3K alpha/mTOR

Oral

Derived from pan-Class I PI3-kinase ATP competitive inhibitor ZSTK474

I

Advanced malignancies

MLN0128 (INK128)

TORC1/2

Oral

ATP competitive

I,II

Advanced solid and hematological malignancies

OSI-027

TORC1/2

Oral

4,5,7-trisubstituted imidazo[5,1-f] triazine

I

Solid tumor, lymphoma

AZD8055

TORC1/2

Oral

ATP competitive, inhibits kinase activity

I

Advanced cancers

AZD2014

TORC1/2

Oral

ATP competitive

I/II

Advanced solid cancers

CC-223

TORC1/2

Oral

ATP competitive

I/II

MM, DLBCL, NHL, solid cancers

ME-344 (NV-128

mTOR

IV

Isoflavone derivative

I

Solid tumors

ABTL0812

TORC1/2, DHFR

Oral

Lipid analogue

I

Advanced tumors

CUDC-907

PI3K/HDAC

Oral

I

Advanced solid tumors, MM