Targets & Mechanisms: Putting SMYD3 on the MAP 

 

Table 1. Selected MAPK pathway compounds in cancer.

Source: BCIQ: BioCentury Online Intelligence

Company

Compound

Indication

Target

Status

Amgen Inc. (NASDAQ:AMGN)

Nexavar sorafenib

Advanced cancers including colorectal, liver, breast, renal and ovarian cancers

CRAF (RAF1); VEGF receptor

Marketed

GlaxoSmithKline plc (LSE:GSK; NYSE:GSK)

Tafinlar dabrafenib

Melanoma with a BRAF V600E or V600K mutation

BRAF

Marketed

Mekinist trametinib

Melanoma with a BRAF V600E or V600K mutation

MAP kinase kinase 1 (MAP2K1; MEK1); MEK2 (MAP2K2)

Marketed

Roche (SIX:ROG; OTCQX:RHHBY); Daiichi Sankyo Co. Ltd. (Tokyo:4568); Chugai Pharmaceutical Co. Ltd. (Tokyo:4519)

Zelboraf vemurafenib

Melanoma with a BRAF V600E mutation

BRAF

Marketed

Amgen

Nexavar sorafenib

Thyroid cancers

CRAF; VEGF receptor

Approved

GlaxoSmithKline

Tafinlar dabrafenib plus Mekinist trametinib

Melanoma with a BRAF V600E or V600K mutation

MEK1; MEK2; BRAF

Registration

Amgen

Nexavar sorafenib

Breast, ovarian and liver cancers; colorectal cancer (CRC)

CRAF; VEGF receptor

Phase III

AstraZeneca plc (LSE:AZN; NYSE:AZN); Array BioPharma Inc. (NASDAQ:ARRY)

Selumetinib (AZD6244)

Non-small cell lung cancer (NSCLC)

MEK1; MEK2

Phase III

Exelixis Inc. (NASDAQ:EXEL); Genentech Inc. unit of Roche

Cobimetinib (RG7421)

Melanoma with a BRAF V600E mutation

MEK1; MEK2

Phase III

GlaxoSmithKline

Tafinlar dabrafenib

Solid tumors with BRAF mutation

BRAF

Phase III

Novartis AG (NYSE:NVS; SIX:NOVN)

Encorafinib (LGX818)

Melanoma with BRAF mutations

BRAF

Phase III

Novartis; Array BioPharma

Binimetinib (MEK162)

Melanoma with BRAF mutations; ovarian cancer

MEK1; MEK2

Phase III

AstraZeneca; Bayer AG (Xetra:BAYN)

Refametinib (BAY 86-9766)

Liver cancer

MEK1; MEK2

Phase II

AstraZeneca; Array BioPharma

Selumetinib (AZD6244)

Leukemia; melanoma; thyroid cancer; breast cancer; CRC

MEK1; MEK2

Phase II

GlaxoSmithKline

Tafinlar dabrafenib

NSCLC with BRAF mutations

BRAF

Phase II

Tafinlar dabrafenib plus Mekinist trametinib

CRC

MEK1; MEK2; BRAF

Phase II

Mekinist trametinib

Relapsed or refractory solid tumors

MEK1; MEK2

Phase II

Second-line treatment of NSCLC with K-Ras (KRAS) mutations

Pancreatic cancer

Merck KGaA (Xetra:MRK)

Pimasertib (AS703026)

Melanoma; pancreatic and ovarian cancer

MEK1; MEK2

Phase II

Novartis

Encorafinib (LGX818)

Solid tumors

BRAF

Phase II

Roche; Daiichi Sankyo; Chugai Pharmaceutical

Zelboraf vemurafenib

Thyroid cancer with a BRAF V600E mutation

BRAF

Phase II

AstraZeneca; Bayer

Refametinib (BAY 86-9766)

Pancreatic and biliary duct cancers

MEK1; MEK2

Phase I/II

BioMed Valley Discoveries Inc.

BVD-523

Solid tumors

MAP kinase 1 (MAPK1; ERK-2); MAPK3 (ERK-1)

Phase I/II

GlaxoSmithKline

Tafinlar dabrafenib

Metastatic CRC (mCRC)

BRAF

Phase I/II

Mekinist trametinib

mCRC

MEK1; MEK2

Phase I/II

Solid tumors with BRAF V600 mutations

Novartis

Encorafinib (LGX818)

CRC

BRAF

Phase I/II

(Continues on p. )

Teva Pharmaceutical Industries Ltd. (NYSE:TEVA); Ambit Biosciences Corp. (NASDAQ:AMBI)

CEP-32496

Melanoma

BRAF

Phase I/II

Eli Lilly and Co. (NYSE:LLY); Deciphera Pharmaceuticals LLC

LY3009120 (DP-4978)

Melanoma; CRC

BRAF; CRAF; ARAF

Phase I

Exelixis; Genentech

Cobimetinib (RG7421)

Solid tumors

MEK1; MEK2

Phase I

Merck; BeiGene Co. Ltd.

BeiGene-283

BRAF- or KRAS-mutation-positive cancers

BRAF

Phase I

Pfizer Inc. (NYSE:PFE)

PD-0325901 plus
PF-05212384

Solid tumors

MEK1; MEK2; mammalian target of rapamycin (mTOR; FRAP; RAFT1); phosphoinositide 3-kinase (PI3K)

Phase I

Roche; Chugai Pharmaceutical

RG7304

Solid tumors

MEK1; CRAF

Phase I

RG7167

Solid tumors

MEK1; MEK2

Phase I

Takeda Pharmaceutical Co. Ltd. (Tokyo:4502)

TAK-733

Solid tumors

MEK1; MEK2

Phase I