Details of the Drug

General Information of Drug (ID: DMG1LVA)

• Drug Name: BLZ-945
• Synonyms: CSF-1R inhibitor (bone cancer); CSF-1R inhibitor (bone cancer), Novartis

Indication

Disease Entry	ICD 11	Status	REF
Amyotrophic lateral sclerosis	8B60.0	Phase 2	[1]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 398.5
  Topological Polar Surface Area (xlogp); 3.4
  Rotatable Bond Count (rotbonds); 5
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 7
• Chemical Identifiers:
  Formula: C20H22N4O3S
  IUPAC Name: 4-[[2-[[(1R,2R)-2-hydroxycyclohexyl]amino]-1,3-benzothiazol-6-yl]oxy]-N-methylpyridine-2-carboxamide
  Canonical SMILES: CNC(=O)C1=NC=CC(=C1)OC2=CC3=C(C=C2)N=C(S3)N[C@@H]4CCCC[C@H]4O
  InChI: InChI=1S/C20H22N4O3S/c1-21-19(26)16-10-13(8-9-22-16)27-12-6-7-15-18(11-12)28-20(24-15)23-14-4-2-3-5-17(14)25/h6-11,14,17,25H,2-5H2,1H3,(H,21,26)(H,23,24)/t14-,17-/m1/s1
  InChIKey: ADZBMFGQQWPHMJ-RHSMWYFYSA-N
• Cross-matching ID:
  PubChem CID: 46184986
  CAS Number: 953769-46-5
  TTD ID: D08NDE

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Granulocyte colony-stimulating factor receptor (G-CSF-R)	TTC70AJ	CSF3R_HUMAN	Inhibitor	[3]
Macrophage colony-stimulating factor 1 receptor (CSF1R)	TT7MRDV	CSF1R_HUMAN	Antagonist	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Amyotrophic lateral sclerosis
• ICD Disease Classification: 8B60.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Granulocyte colony-stimulating factor receptor (G-CSF-R)	DTT	CSF3R	2.08E-08	0.36	0.96

References

• [1] ClinicalTrials.gov (NCT04066244) Study of Safety and of the Mechanism of BLZ945 in ALS Patients. U.S. National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] 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: 1719).
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] Clinical pipeline report, company report or official report of Deciphera Pharmaceuticals.
• [8] Clinical pipeline report, company report or official report of Turning Point Therapeutics.
• [9] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [10] Evidence that the granulocyte colony-stimulating factor (G-CSF) receptor plays a role in the pharmacokinetics of G-CSF and PegG-CSF using a G-CSF-R KO model. Pharmacol Res. 2004 Jul;50(1):55-8.
• [11] A glycosylated recombinant human granulocyte colony stimulating factor produced in a novel protein production system (AVI-014) in healthy subjects: a first-in human, single dose, controlled study. BMC Clin Pharmacol. 2009; 9: 2.
• [12] Granulocyte colony-stimulating factor in patients with acute ischemic stroke: results of the AX200 for Ischemic Stroke trial. Stroke. 2013 Oct;44(10):2681-7.
• [13] Survival efficacy of the PEGylated G-CSFs Maxy-G34 and neulasta in a mouse model of lethal H-ARS, and residual bone marrow damage in treated survivors. Health Phys. 2014 Jan;106(1):21-38.
• [14] National Cancer Institute Drug Dictionary (drug id 747694).
• [15] Merck ditches biogeneric. Nat Biotechnol. 2010 Jul;28(7):636.
• [16] Microglial Stimulation of Glioblastoma Invasion Involves Epidermal Growth Factor Receptor (EGFR) and Colony Stimulating Factor 1 Receptor (CSF-1R) Signaling. Mol Med. 2012; 18(1): 519-527.