GtoPdb is requesting financial support from commercial users. Please see our sustainability page for more information.

NXP800   Click here for help

GtoPdb Ligand ID: 14086

Synonyms: CCT361814 | compound 22 [PMID: 37017629] | NXP-800
Compound class: Synthetic organic
Comment: NXP800 (CCT361814) was identified as an orally bioavailable heat shock factor 1 (HSF1) pathway inhibitor in a phenotypic screen [3]. It was proposed for anti-proliferative activity in tumours. Subsequent studies identified NXP800 as an activator of the GCN2 (general control nonderepressible 2) kinase that phosphorylates eukaryotic translation initiation factor 2 alpha (EIF2α) [2]. This activity promotes selective ATF4-mediated transcription of genes involved in the integrated stress response (ISR), ultimately leading to apoptosis of tumour cells [4].
2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 9
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 95.5
Molecular weight 569.63
XLogP 0.57
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

✖
Canonical SMILES CCN1CCN(CC1)CC2=CC=C3C=C(C=CC3=N2)C(=O)NC4=CC(=CC=C4F)NC(=O)C5=CC=C6C(=C5)OCCO6
Isomeric SMILES CCN1CCN(CC1)CC2=NC3=C(C=C2)C=C(C=C3)C(=O)NC4=C(C=CC(=C4)NC(=O)C5=CC6=C(C=C5)OCCO6)F
InChI InChI=1S/C32H32FN5O4/c1-2-37-11-13-38(14-12-37)20-25-6-3-21-17-22(4-9-27(21)34-25)32(40)36-28-19-24(7-8-26(28)33)35-31(39)23-5-10-29-30(18-23)42-16-15-41-29/h3-10,17-19H,2,11-16,20H2,1H3,(H,35,39)(H,36,40)
InChI Key UBALMDIKIGDHJW-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Carlson DM, Kuipers H, Abdelrhaman A, Jessen E, Kalil JR, Sample J, Tomlinson J, Truty M, Smoot R. (2024)
Abstract 2098: A novel GCN2 kinase activator demonstrates therapeutic efficacy in preclinical PDX models of human cholangiocarcinoma.
Cancer Research, 84 (6_Supplement): 2098. DOI: 10.1158/1538-7445.AM2024-2098
2. Kuipers H, Larson JJ, Conboy CB, Ahn DH, Bekaii-Saab T, Wu C, Sonbol MB, Ilyas SI, Gores GJ, Smoot RL et al.. (2025)
A Phase 1 study of the novel GCN2 kinase activator NXP800 in patients with advanced cholangiocarcinoma.
Future Oncol, 21 (21): 2723-2730. [PMID:40717483]
3. Pasqua AE, Sharp SY, Chessum NEA, Hayes A, Pellegrino L, Tucker MJ, Miah A, Wilding B, Evans LE, Rye CS et al.. (2023)
HSF1 Pathway Inhibitor Clinical Candidate (CCT361814/NXP800) Developed from a Phenotypic Screen as a Potential Treatment for Refractory Ovarian Cancer and Other Malignancies.
J Med Chem, 66 (8): 5907-5936. [PMID:37017629]
4. Zhao C, Chen J, Tian L, Wen Y, Wu M, Tang L, Zhou A, Xie W, Dong T. (2024)
Gandouling ameliorates liver injury in Wilson's disease through the inhibition of ferroptosis by regulating the HSF1/HSPB1 pathway.
J Cell Mol Med, 28 (17): e70018. [PMID:39223962]