Rociletinib

Cancelled developmental cancer drug

L01EB05 (WHO)

Identifiers

IUPAC name

N-(3-{[2-{[4-(4-Acetyl-1-piperazinyl)-2-methoxyphenyl]amino}-5-(trifluoromethyl)-4-pyrimidinyl]amino}phenyl)acrylamide

CAS Number

1374640-70-6

PubChem CID

57335384

DrugBank

DB11907

ChemSpider

30646712

UNII

72AH61702G

KEGG

D10858

CompTox Dashboard (EPA)

DTXSID801025958

Chemical and physical dataFormulaC₂₇H₂₈F₃N₇O₃Molar mass555.562 g·mol⁻¹3D model (JSmol)

Interactive image

SMILES

CC(=O)N1CCN(CC1)c2ccc(c(c2)OC)Nc3ncc(c(n3)Nc4cccc(c4)NC(=O)C=C)C(F)(F)F

InChI

InChI=1S/C27H28F3N7O3/c1-4-24(39)32-18-6-5-7-19(14-18)33-25-21(27(28,29)30)16-31-26(35-25)34-22-9-8-20(15-23(22)40-3)37-12-10-36(11-13-37)17(2)38/h4-9,14-16H,1,10-13H2,2-3H3,(H,32,39)(H2,31,33,34,35)
Key:HUFOZJXAKZVRNJ-UHFFFAOYSA-N

Rociletinib is a medication developed to treat non-small cell lung carcinomas with a specific mutation. It is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor.^[1] It was being developed by Clovis Oncology as a potential treatment for non-small-cell lung cancer.^[1] In May 2016, development of rociletinib was halted, along with its associated clinical trials, and Clovis Oncology withdrew its marketing authorisation application from the European Medicines Agency.^[1]

References

^ ^a ^b ^c Van Der Steen N, Caparello C, Rolfo C, Pauwels P, Peters GJ, Giovannetti E (2016). "New developments in the management of non-small-cell lung cancer, focus on rociletinib: what went wrong?". OncoTargets and Therapy. 9: 6065–6074. doi:10.2147/OTT.S97644. PMC 5063481. PMID 27785053.

Targeted cancer therapy / antineoplastic agents (L01)

CI monoclonal antibodies ("-mab")

Receptor tyrosine kinase	ErbB: HER1/EGFR (Cetuximab Panitumumab) HER2/neu (Pertuzumab, Trastuzumab (+hyaluronidase) Trastuzumab emtansine Trastuzumab deruxtecan)
Others for solid tumors	EpCAM (Catumaxomab Edrecolomab) VEGF-A (Bevacizumab)
Leukemia/lymphoma	lymphoid: CD3 (Glofitamab, Elranatamab, Mosunetuzumab), CD20 (Glofitamab Ibritumomab Mosunetuzumab Obinutuzumab Ofatumumab Rituximab Tositumomab), CD30 (Brentuximab), CD52 (Alemtuzumab) myeloid: CD33 (Gemtuzumab ozogamicin)
Other	Amivantamab Atezolizumab Avelumab Belantamab mafodotin Bermekimab Blinatumomab Cemiplimab Daratumumab Dinutuximab beta Dostarlimab Durvalumab Elotuzumab Enfortumab vedotin Epcoritamab Inotuzumab ozogamicin Ipilimumab Isatuximab Loncastuximab tesirine Mirvetuximab soravtansine Mogamulizumab Moxetumomab pasudotox Naxitamab Necitumumab Nivolumab Olaratumab Oportuzumab monatox Pembrolizumab Polatuzumab vedotin Prolgolimab Ramucirumab Retifanlimab Sabatolimab Sacituzumab govitecan Serplulimab Sugemalimab Tafasitamab Talquetamab Tarlatamab Teclistamab Tislelizumab Tisotumab vedotin Toripalimab Tremelimumab

Tyrosine kinase inhibitors ("-nib")

Receptor tyrosine kinase	ErbB: HER1/EGFR (Afatinib Brigatinib Dacomitinib Erlotinib Gefitinib Icotinib Mobocertinib Olmutinib Osimertinib Rociletinib Vandetanib) HER1/EGFR and HER2/neu Lapatinib Neratinib Tucatinib RTK class III: C-kit and PDGFR (Avapritinib Axitinib Masitinib Pazopanib Ripretinib Sorafenib Sunitinib Toceranib) FLT3 (Lestaurtinib, Gilteritinib (AXL, ALK, LTK)) VEGFR Axitinib Cediranib Fruquintinib Lenvatinib Nintedanib Pazopanib Regorafenib Semaxanib Sorafenib Sunitinib Tivozanib Toceranib Vandetanib ALK Alectinib Brigatinib Ceritinib RET inhibitors: Entrectinib (ALK, ROS1, NTRK), Futibatinib (FGFR2), Infigratinib, Larotrectinib (NTRK), Pemigatinib (FGFR), Pralsetinib, Repotrectinib (ROS1, TRK, ALK), Selpercatinib (VEGFR, FGFR), Vandetanib (VEGFR, EGFR). c-MET inhibitors: Cabozantinib (VEGFR), Capmatinib, Crizotinib (ALK)
Non-receptor	bcr-abl Asciminib Bosutinib Dasatinib Imatinib Nilotinib Ponatinib Radotinib Src (Bosutinib Dasatinib) Janus kinase Baricitinib Fedratinib Filgotinib Lestaurtinib Momelotinib Pacritinib Ruxolitinib MAP2K Binimetinib Cobimetinib Selumetinib Trametinib EML4-ALK Crizotinib Entrectinib Lorlatinib Bruton's Acalabrutinib Ibrutinib Pirtobrutinib Zanubrutinib

Receptor tyrosine kinase

HER1/EGFR and HER2/neu

RTK class III: C-kit and PDGFR (Avapritinib
Axitinib
Masitinib
Pazopanib
Ripretinib
Sorafenib
Sunitinib
Toceranib)
FLT3 (Lestaurtinib, Gilteritinib (AXL, ALK, LTK))

VEGFR
- Axitinib
- Cediranib
- Fruquintinib
- Lenvatinib
- Nintedanib
- Pazopanib
- Regorafenib
- Semaxanib
- Sorafenib
- Sunitinib
- Tivozanib
- Toceranib
- Vandetanib

ALK

RET inhibitors: Entrectinib (ALK, ROS1, NTRK), Futibatinib (FGFR2), Infigratinib, Larotrectinib (NTRK), Pemigatinib (FGFR), Pralsetinib, Repotrectinib (ROS1, TRK, ALK), Selpercatinib (VEGFR, FGFR), Vandetanib (VEGFR, EGFR).

c-MET inhibitors: Cabozantinib (VEGFR), Capmatinib, Crizotinib (ALK)

Non-receptor

bcr-abl
- Asciminib
- Bosutinib
- Dasatinib
- Imatinib
- Nilotinib
- Ponatinib
- Radotinib

Src (Bosutinib
Dasatinib)

Janus kinase

MAP2K

EML4-ALK

Bruton's

Other

fusion protein against VEGF (Aflibercept)
proapoptotic peptide against ANXA2 and prohibitin (Adipotide)
exotoxin against IL-2 (Denileukin diftitox)
mTOR inhibitors
- Everolimus
- Ridaforolimus
- Temsirolimus
hedgehog inhibitors
- Glasdegib
- Sonidegib
- Vismodegib
CDK inhibitors
- Abemaciclib
- Dalpiciclib
- Palbociclib
- Ribociclib
- Trilaciclib
KRAS inhibitors
- Adagrasib
- Sotorasib
Cabozantinib
Capmatinib
Entrectinib
Erdafitinib
Gilteritinib
Larotrectinib
Lenvatinib
Masitinib
Midostaurin
Nintedanib
Pazopanib
Pemigatinib
Pexidartinib
Quizartinib
Regorafenib
Ripretinib
Sorafenib
Sunitinib
Tebentafusp
Tepotinib
Vandetanib
Venetoclax

Growth factor receptor modulators

Angiopoietin

Agonists: Angiopoietin 1
Angiopoietin 4

Antagonists: Angiopoietin 2
Angiopoietin 3

Kinase inhibitors: Altiratinib
CE-245677
Rebastinib

Antibodies: Evinacumab (against angiopoietin 3)
Nesvacumab (against angiopoietin 2)

CNTF

Agonists: Axokine
CNTF
Dapiclermin

EGF (ErbB)

EGF (ErbB1/HER1)	Agonists: Amphiregulin Betacellulin EGF (urogastrone) Epigen Epiregulin Heparin-binding EGF-like growth factor (HB-EGF) Murodermin Nepidermin Transforming growth factor alpha (TGFα) Kinase inhibitors: Afatinib Agerafenib Brigatinib Canertinib Dacomitinib Erlotinib Gefitinib Grandinin Icotinib Lapatinib Neratinib Osimertinib Vandetanib WHI-P 154 Antibodies: Cetuximab Depatuxizumab Depatuxizumab mafodotin Futuximab Imgatuzumab Matuzumab Necitumumab Nimotuzumab Panitumumab Zalutumumab
ErbB2/HER2	Agonists: Unknown/none Antibodies: Ertumaxomab Pertuzumab Trastuzumab Trastuzumab deruxtecan Trastuzumab duocarmazine Trastuzumab emtansine Kinase inhibitors: Afatinib Lapatinib Mubritinib Neratinib Tucatinib
ErbB3/HER3	Agonists: Neuregulins (heregulins) (1, 2, 6 (neuroglycan C)) Antibodies: Duligotumab Patritumab Seribantumab
ErbB4/HER4	Agonists: Betacellulin Epigen Heparin-binding EGF-like growth factor (HB-EGF) Neuregulins (heregulins) (1, 2, 3, 4, 5 (tomoregulin, TMEFF))

FGF

FGFR1	Agonists: Ersofermin FGF (1, 2 (bFGF), 3, 4, 5, 6, 8, 10 (KGF2), 20) Repifermin Selpercatinib Trafermin Velafermin
FGFR2	Agonists: Ersofermin FGF (1, 2 (bFGF), 3, 4, 5, 6, 7 (KGF), 8, 9, 10 (KGF2), 17, 18, 22) Palifermin Repifermin Selpercatinib Sprifermin Trafermin Antibodies: Aprutumab Aprutumab ixadotin Kinase inhibitors: Infigratinib
FGFR3	Agonists: Ersofermin FGF (1, 2 (bFGF), 4, 8, 9, 18, 23) Selpercatinib Sprifermin Trafermin Antibodies: Burosumab (against FGF23)
FGFR4	Agonists: Ersofermin FGF (1, 2 (bFGF), 4, 6, 8, 9, 19) Trafermin
Unsorted	Agonists: FGF15/19

HGF (c-Met)

Agonists: Fosgonimeton
Hepatocyte growth factor

Potentiators: Dihexa (PNB-0408)

Kinase inhibitors: Altiratinib
AM7
AMG-458
Amuvatinib
BMS-777607
Cabozantinib
Capmatinib
Crizotinib
Foretinib
Golvatinib
INCB28060
JNJ-38877605
K252a
MK-2461
PF-04217903
PF-2341066
PHA-665752
SU-11274
Tivantinib
Volitinib

IGF

IGF-1	Agonists: des(1-3)IGF-1 Insulin-like growth factor-1 (somatomedin C) IGF-1 LR3 Insulin-like growth factor-2 (somatomedin A) Insulin Mecasermin Mecasermin rinfabate Kinase inhibitors: BMS-754807 Linsitinib NVP-ADW742 NVP-AEW541 OSl-906 Antibodies: AVE-1642 Cixutumumab Dalotuzumab Figitumumab Ganitumab Robatumumab R1507 Teprotumumab Xentuzumab (against IGF-1 and IGF-2)
IGF-2	Agonists: Insulin-like growth factor-2 (somatomedin A) Antibodies: Dusigitumab Xentuzumab (against IGF-1 and IGF-2)
Others	Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7) Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) Trofinetide

LNGF (p75^NTR)

Antagonists: ALE-0540
Dexamethasone
EVT-901 (SAR-127963)
Testosterone

Antibodies: Against NGF: ABT-110 (PG110)
ASP-6294
Fasinumab
Frunevetmab
Fulranumab
MEDI-578
Ranevetmab
Tanezumab

Aptamers: Against NGF: RBM-004

Decoy receptors: LEVI-04 (p75^NTR-Fc)

PDGF

Agonists: Becaplermin
Platelet-derived growth factor (A, B, C, D)

RET (GFL)

GFRα1	Agonists: Glial cell line-derived neurotrophic factor (GDNF) Liatermin Kinase inhibitors: Vandetanib
GFRα2	Agonists: Neurturin (NRTN) Kinase inhibitors: Vandetanib
GFRα3	Agonists: Artemin (ARTN) Kinase inhibitors: Vandetanib
GFRα4	Agonists: Persephin (PSPN) Kinase inhibitors: Vandetanib
Unsorted	Kinase inhibitors: Agerafenib

SCF (c-Kit)

Agonists: Ancestim
Stem cell factor

TGFβ

See here instead.

Trk

TrkA	Agonists: Amitriptyline BNN-20 BNN-27 Cenegermin DHEA DHEA-S Gambogic amide NGF Tavilermide Antagonists: ALE-0540 Dexamethasone FX007 Testosterone Negative allosteric modulators: VM-902A Kinase inhibitors: Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib Milciclib ONO-4474 ONO-5390556 PLX-7486 Rebastinib SNA-120 (pegylated K252a)) Antibodies: Against TrkA: GBR-900; Against NGF: ABT-110 (PG110) ASP-6294 Fasinumab Frunevetmab Fulranumab MEDI-578 Ranevetmab Tanezumab Aptamers: Against NGF: RBM-004 Decoy receptors: ReN-1820 (TrkAd5)
TrkB	Agonists: 3,7-DHF 3,7,8,2'-THF 4'-DMA-7,8-DHF 7,3'-DHF 7,8-DHF 7,8,2'-THF 7,8,3'-THF Amitriptyline BDNF BNN-20 Deoxygedunin Deprenyl Diosmetin DMAQ-B1 HIOC LM22A-4 N-Acetylserotonin NT-3 NT-4 Norwogonin (5,7,8-THF) R7 R13 TDP6 Antagonists: ANA-12 Cyclotraxin B Gossypetin (3,5,7,8,3',4'-HHF) Ligands: DHEA Kinase inhibitors: Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486
TrkC	Agonists: BNN-20 DHEA NT-3 Kinase inhibitors: Altiratinib AZD-6918 CE-245677 CH-7057288 DS-6051 Entrectinib GZ-389988 K252a Larotrectinib Lestaurtinib ONO-4474 ONO-5390556 PLX-7486