Details of the Drug

General Information of Drug (ID: DML10K3)

• Drug Name: SF1126
• Synonyms: CC-1126; SF-1126; L-Serine, N2-(1,4-dioxo-4-((4-(4-oxo-8-phenyl-4H-1-benzopyran-2-yl)morpholinium-4-yl)methoxy)butyl)-L-arginylglycyl-L-alpha-aspartyl-, inner salt

Indication

Disease Entry	ICD 11	Status	REF
Head and neck cancer	2D42	Phase 2	[1]
Hepatocellular carcinoma	2C12.02	Phase 1	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

• Therapeutic Class: Anticancer Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 4:
  Molecular Weight (mw); 852.8
  Topological Polar Surface Area (xlogp); -1.5
  Rotatable Bond Count (rotbonds); 22
  Hydrogen Bond Donor Count (hbonddonor); 8
  Hydrogen Bond Acceptor Count (hbondacc); 15
• Chemical Identifiers:
  Formula: C39H48N8O14
  IUPAC Name: (2S)-2-[[(2S)-3-carboxy-2-[[2-[[(2S)-5-(diaminomethylideneamino)-2-[[4-oxo-4-[[4-(4-oxo-8-phenylchromen-2-yl)morpholin-4-ium-4-yl]methoxy]butanoyl]amino]pentanoyl]amino]acetyl]amino]propanoyl]amino]-3-hydroxypropanoate
  Canonical SMILES: C1COCC[N+]1(COC(=O)CCC(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)[O-])C2=CC(=O)C3=C(O2)C(=CC=C3)C4=CC=CC=C4
  InChI: InChI=1S/C39H48N8O14/c40-39(41)42-13-5-10-26(36(55)43-20-31(51)45-27(18-33(52)53)37(56)46-28(21-48)38(57)58)44-30(50)11-12-34(54)60-22-47(14-16-59-17-15-47)32-19-29(49)25-9-4-8-24(35(25)61-32)23-6-2-1-3-7-23/h1-4,6-9,19,26-28,48H,5,10-18,20-22H2,(H9-,40,41,42,43,44,45,46,50,51,52,53,55,56,57,58)/t26-,27-,28-/m0/s1
  InChIKey: SVNJBEMPMKWDCO-KCHLEUMXSA-N
• Cross-matching ID:
  PubChem CID: 66577114
  DrugBank ID: DB05210
  TTD ID: D03NJY

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
PI3-kinase gamma (PIK3CG)	TTHBTOP	PK3CG_HUMAN	Modulator	[3], [4]
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[1]

Molecular Expression Atlas of This Drug

• The Studied Disease: Head and neck cancer
• ICD Disease Classification: 2D42

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
PI3-kinase gamma (PIK3CG)	DTT	PIK3CG	1.98E-01	-0.05	-0.55

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026065)
• [3] An integrin-targeted, pan-isoform, phosphoinositide-3 kinase inhibitor, SF1126, has activity against multiple myeloma in vivo.Cancer Chemother Pharmacol.2013 Apr;71(4):867-81.
• [4] Pan-PI-3 kinase inhibitor SF1126 shows antitumor and antiangiogenic activity in renal cell carcinoma.Cancer Chemother Pharmacol. 2015 Mar;75(3):595-608.
• [5] Knockouts model the 100 best-selling drugs--will they model the next 100 Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
• [6] Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Mammalian target of rapamycin, its mode of action and clinical response in metastatic clear cell carcinoma. Gan To Kagaku Ryoho. 2009 Jul;36(7):1076-9.
• [9] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2109).
• [10] Natural products to drugs: natural product-derived compounds in clinical trials. Nat Prod Rep. 2008 Jun;25(3):475-516.
• [11] A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
• [12] Dramatic suppression of colorectal cancer cell growth by the dual mTORC1 and mTORC2 inhibitor AZD-2014. Biochem Biophys Res Commun. 2014 Jan 10;443(2):406-12.
• [13] BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110 and p110 activities in tumor cell lines and xenograft models.Mol Cancer Ther.2013 Nov;12(11):2319-30.
• [14] PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013 Nov 21;20(11):1364-74.
• [15] Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
• [16] Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3K and Plk1 pathways, in adult patients with advanced solid malignancies. Clin Cancer Res. 2014 Mar 15;20(6):1656-65.
• [17] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2155).
• [18] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2156).
• [19] First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer. Clin Cancer Res. 2015 Apr 15;21(8):1888-95.