IP Library › Granted Patent US 12,564,578
Granted Patent B2
US 12,564,578 · App. 17/682,856 · Granted Mar 3, 2026

Collagen P4H1 inhibitor and its use

Inventors: Ren Xu (Lexington, KY); Shike Wang (Lexington, KY)
Assignee: University of Kentucky Research Foundation
A61K31/4365A61K31/216A61K31/337A61K31/404G01N33/582
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Quick Facts
Patent No.
US 12,564,578
App. No.
17/682,856
Granted
Mar 3, 2026
Kind
B2
Abstract

The present invention relates to a methods for modulating Collagen Prolyl 4-hydroxylase (C-P4H1) in a cell. The present invention further relates to methods for inhibiting a cancer cell. The instant invention also relates to methods for identifying modulators of Collagen Prolyl 4-hydroxylase (C-P4H1).

Claims (10)

1 . A method of screening for modulators of C-P4H1, comprising:

(a) expressing a P4H1 complex in a eukaryotic cell;

(b) purifying the P4H1 complex;

(c) adding the purified P4H1 complex to a well of a high throughput assay plate;

(d) adding peptide substrate GlyProProGlyOEt, FeSO 4 , catalase, ascorbate, and α-ketoglutarate to the well of the high throughput assay plate;

(e) adding a test molecule or control to the well of the high throughput assay plate;

(f) adding 3-oxoacid CoA-transferase (SCOT) and succinyl CoA ligase (SCS), in the presence of acetoacetyl-CoA to convert succinate into ATP to the well of the high throughput assay plate;

(g) adding luciferase to convert ATP into light energy to the well of the high throughput assay plate;

(h) measuring luminescence of the well of the high throughput assay plate; and

(i) identifying a molecule as a modulator of P4H1 when the molecule increases luminescence of the well relative to negative control or decreases luminescence of the well relative to positive control.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 28, 2022
From: XU, REN; WANG, SHIKE
To: UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION
Reel/Frame 059121/0880 →
Continuity (3)
Continuation In Part PCTUS2020048582 · Aug 28, 2020
Provisional Application 62893002 · Aug 28, 2019
Related Publication 20220175742A1 · Jun 9, 2022
References Cited (28)
US 9289415B2 · Shi et al. · 2016 [cited by applicant]
US 9677117B2 · Alves et al. · 2017 [cited by applicant]
US 10130590B2 · Frank et al. · 2018 [cited by applicant]
US 20160280701A1 · Raines et al. · 2016 [cited by applicant]
US 20170304388A1 · Chen et al. · 2017 [cited by applicant]
WO WO2019060742 · 2019 [cited by applicant]
Promega Website https://www.promega.com/products/epigenetics/methylation-analysis/succinate-glo-jmjc-demethylase-hydroxylase-assay/?catNum=V7990&accordion0=0 Accessed Jun. 10, 2025 (Year: 2025). [cited by examiner]
Oertli, et al., Perioperative and postoperative tranexamic acid reduces the local wound complication rate after surgery for breast cancer, British Journal of Surgery 1994, 81, pp. 856-859. [cited by applicant]
Catino, et al., Amifostine as chemoprotectant in metastatic breast cancer patients treated with doxorubicin, Oncology reports, 2003, pp. 163-167. [cited by applicant]
Pandya, et al., Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial, Lancet 2005; 366: 818-24. [cited by applicant]
Martin, et al., In vitro inhibitory effects of atorvastatin on cardiac fibroblasts: implications for ventricular remodeling, Clinical and Experimental Pharmacology and Physiology (2005) 32, 697-701. [cited by applicant]
Sastry, et al., Epinephrine protects cancer cells from apoptosis via activation of cAMP-dependent protein kinase and BAD phosphorylation, The Journal of Biological Chemistry vol. 282, No. 19, pp. 14094-14100, May 11, 20… [cited by applicant]
Wang, et al, Antipsychotic drugs inhibit the function of breast cancer resistance protein, Basic & Clinical Pharmacology & Toxicology, 103, 336-341. [cited by applicant]
Li, et al., Fenofibrate induces apoptosis of triple-negative breast cancer cells via activation of NF-κB pathway, BMC Cancer 2014, 14:96, 1-13. [cited by applicant]
Romermann, et al, The antiepileptic drug lamotrigine is a substrate of mouse and human breast cancer resistance protein (ABCG2), Neuropharmacology 93 (2015) pp. 7-14. [cited by applicant]
Desai, et al, Statins and breast cancer stage and mortality in the Women's Health Initiative, Cancer Causes Control (2015) 26:529-539. [cited by applicant]
Fiorillo, et al, Repurposing atovaquone: Targeting mitochondrial complex III, Oncotarget, vol. 7, No. 23, 2016. [cited by applicant]
Provenzano, P. P.; Inman, D. R.; Eliceiri, K. W.; Knittel, J. G.; Yan, L.; Rueden, C. T.; White, J. G.; Keely, P. J., Collagen density promotes mammary tumor initiation and progression. BMC Med 2008, 6, 11. [cited by applicant]
Gorres, K. L.; Raines, R. T., Prolyl 4-hydroxylase. Crit Rev Biochem Mol Biol 2010, 45 (2), 106-24. [cited by applicant]
Zhang, H.; Fredericks, T.; Xiong, G.; Qi, Y.; Rychahou, P. G.; Li, J. D.; Pihlajaniemi, T.; Xu, W.; Xu, R., Membrane associated collagen XIII promotes cancer metastasis and enhances anoikis resistance. Breast Cancer Res… [cited by applicant]
Hanker, A. B.; Estrada, M. V.; Bianchini, G.; Moore, P. D.; Zhao, J.; Cheng, F.; Koch, J. P.; Gianni, L.; Tyson, D. R.; Sanchez, V.; Rexer, B. N.; Sanders, M. E.; Zhao, Z.; Stricker, T. P.; Arteaga, C. L., Extracellular… [cited by applicant]
Xiong, G.; Stewart, R. L.; Chen, J.; Gao, T.; Scott, T. L.; Samayoa, L. M.; O'Connor, K.; Lane, A. N.; Xu, R., Collagen prolyl 4-hydroxylase 1 is essential for HIF-1alpha stabilization and TNBC chemoresistance. Nat Comm… [cited by applicant]
Bickel, M.; Baringhaus, K. H.; Gerl, M.; Gunzler, V.; Kanta, J.; Schmidts, L.; Stapf, M.; Tschank, G.; Weidmann, K.; Werner, U., Selective inhibition of hepatic collagen accumulation in experimental liver fibrosis in ra… [cited by applicant]
Gorres, K. L.; Raines, R. T., Direct and continuous assay for prolyl 4-hydroxylase. Anal Biochem 2009, 386 (2), 181-5. [cited by applicant]
Vasta, J. D.; Andersen, K. A.; Deck, K. M.; Nizzi, C. P.; Eisenstein, R. S.; Raines, R. T., Selective Inhibition of Collagen Prolyl 4-Hydroxylase in Human Cells. ACS Chem Biol 2016, 11 (1), 193-9. [cited by applicant]
Guo, H. F.; Cho, E. J.; Devkota, A. K.; Chen, Y.; Russell, W.; Phillips, G. N., Jr.; Yamauchi, M.; Dalby, K. N.; Kurie, J. M., A scalable lysyl hydroxylase 2 expression system and luciferase-based enzymatic activity ass… [cited by applicant]
Kivirikko, K. I.; Kishida, Y.; Sakakibara, S.; Prockop, D. J., Hydroxylation of (X-Pro-Gly)n by protocollagen proline hydroxylase. Effect of chain length, helical conformation and amino acid sequence in the substrate. B… [cited by applicant]
TM488 Technical Manual, entitled “Succinate-GloTM JmjC Demethylase/Hydroxylase Assay,” Mar. 2017, from Promega Corporation. [cited by applicant]