Table 1.

Targeted therapy in combination trials in cutaneous advanced melanoma (52, 102, 103)

DrugMolecular targetPubChem ID
MAPK Pathway
 Dabrafenib (GSK2118436)BRAF V60044462760
 Encorafenib (LGX818)BRAF V60050922675
 Vemurafenib (PLX4032)BRAF V60042611257
 Cobimetinib (GDC-0973, XL-518)MEK16222096
 Binimetinib (MEK162)MEK10288191
 PD-0325901MEK9826528
 Pimasertib (MSC-1936369B, AS-703026)MEK44187362
 Refametinib (BAY 86-9766)MEK44182295
 Selumetinib (AZD6244)MEK10127622
 Trametinib (GSK1120212)MEK11707110
 WX-554MEKNot listed
 RO5126766 (CH5126766)Dual RAF/MEK16719221
PI3K Pathway
 Buparlisib (BKM120)Pan-PI3K16654980
 Copanlisib (BAY-80-6946)Pan-PI3K24989044
 Pictilisib (GDC-0941)Pan-PI3K17755052
 Sonolisib (PX-866)Pan-PI3K9849735
 Alpelisib (BYL-719)PI3K-α56649450
 SAR260301PI3K-β49854424
 WX-037PI3KaNot listed
 Everolimus (RAD001)mTOR6442177
 Temsirolimus (CCI-779)mTOR6918289
 Omipalisib (GSK-2126458) (104)Dual PI3K/mTOR25167777
 Dactolisib (BEZ235)Dual PI3K/mTOR11977753
 PF-04691502Dual PI3K/mTOR25033539
 Voxtalisib (SAR245409)Dual PI3K/mTOR49867926
 Afuresertib (GSK2110183)AKT46843057
 Ipatasertib (GDC-0068)AKT74078320
 MK-2206AKT24964624
 Uprosertib (GSK2141795)AKT51042438
Multi-RTK and RAF
 Sorafenib (BAY43-9006)RAF kinases and VEGF receptors216239
 RAF265BRAF and VEGFR-211656518
 Regorafenib (BAY 73-4506)VEGFR-2 and -3, RET, KIT, PDGFR, RAF kinases11167602
RTK/GFRs Pathways
 Cabozantinib (XL184)RET, MET, VEGFR-1, -2, and -3, KIT, TRKB, FLT-3, AXL, TIE-225102847
 Lenvatinib (E7080)VEGF-1, -2, -3, FGFR-1, -2, -3, -4, PDGFR-α, KIT, RET9823820
 Pazopanib (GW786034B)VEGFR-1, -2, -3, PDGFR-α, -β, c-KIT10113978
 CetuximabEGFR85668777
 Capmatinib (INC280)HGFR (c-MET)25145656
 GolvatinibHGFR (c-MET), VEGFR216118392
 Onartuzumab (MetMAb)HGFR (c-MET)Not listed
 Tivantinib (ARQ-197)HGFR (c-MET)11494412
 Ganitumab (AMG 479)IGF-1RNot listed
 BevacizumabVEGFNot listed
 MEHD7945ADual EGFR/HER3 (ErbB3)Not listed
 BGJ398 (NVP-BGJ398)pan-FGFR53235510
CDK Pathway
 Palbociclib (PD-0332991)CDK4/65330286
 Ribociclib (LEE011)CDK4/644631912
 Voruciclib (P1446A-05)CDK4/667409219
  • Abbreviations: AKT, v-Akt murine thymoma viral oncogene/protein kinase-b; CDK, cyclin-dependent kinase; c-MET, hepatocyte receptor growth receptor (also HGFR); HGFR, hepatocyte growth factor receptor (also c-MET); PDGFR, platelet-derived growth factor receptor; TRKB, tropomyosin receptor kinase B.

  • aPI3K specificity has not been reported.