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- || Givlaari (givosiran) / Alnylam
Review, Journal: Givosiran: a targeted treatment for acute intermittent porphyria. (Pubmed Central) - Dec 7, 2024
Common side effects include injection site reactions, hyperhomocysteinemia, and abnormalities of liver and renal biochemistries. This article reviews the studies that led to givosiran approval, discusses real-world clinical data, and highlights remaining questions in the treatment of AHP.
- | paclitaxel / Generic mfg.
Journal: Electroacupuncture Facilitates Vascular Normalization by Inhibiting Glyoxalase1 in Endothelial Cells to Attenuate Glycolysis and Angiogenesis in Triple-Negative Breast Cancer. (Pubmed Central) - Aug 15, 2024
The timely integration of peri-tumoral electroacupuncture amplified the anti-tumor efficacy of paclitaxel...The study using the Glo1-silenced zebrafish model further supported the role of Glo1 in vascular development. This study underscores the pivotal role of Glo1 in peri-tumoral electroacupuncture, spotlighting a promising avenue for enhancing vascular normalization and improving TNBC treatment outcomes.
- dordaviprone (ONC201) / Chimerix, nesuparib (JPI-547) / Jeil
ClpP-dependent and -independent activation of HRI kinase by small molecules (Section 25) - Mar 5, 2024 - Abstract #AACR2024AACR_2729;
We are further investigating the targets of PG3 and the signaling pathway that leads to PG3-induced activation of HRI. Our results suggest that different small molecule inducers of the ISR such as ONC201 and PG3 can achieve an anti-tumor effect through different pathways converging on kinase HRI ultimately leading to ATF4 activation and tumor cell death.
- Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute
Heme promotes venetoclax resistance in multiple myeloma (In Person) - Sep 10, 2023 - Abstract #IMW2023IMW_479;
Our results mechanistically illustrate a role for heme in modulating proximity to the apoptotic threshold with broader translational implications. Heme can be sourced from both extrinsic sources such as through diet and cells in the extrinsic milieu or through de novo synthesis, underscoring the importance of investigating heme metabolism in MM therapy.
- metformin / Generic mfg.
The heme synthesis-export system is a druggable pan-cancer essentiality. (Poster and Exhibition Hall) - Jun 13, 2023 - Abstract #EACR2023EACR_568;
The collected data prove that ALA administration results in heme accumulation and ALAS1 downmodulation, phenocopying the metabolic reprogramming, compromised cell proliferation and increased sensitivity to metformin observed upon FLVCR1a silencing.ConclusionAltogether, these results support the targeting of the FLVCR1a-ALAS1 axis as a promising strategy to counteract tumor growth and to increase the sensitivity to antitumor agents targeting oxidative metabolism. Finally, they sustain ALA repositioning as anticancer agent.
- dordaviprone (ONC201) / Chimerix
TIC10/ONC201 activates ClpP to degrade ALAS1 while PG3 does not degrade ALAS1 in pathway to HRI, ATF4 and CHOP activation leading to tumor cell death (Section 16; Poster Board #5) - Mar 14, 2023 - Abstract #AACR2023AACR_7297;
We are further investigating the signaling pathway that leads to PG3-induced activation of HRI. Our results suggest that different small molecule inducers of the ISR such as ONC201 and PG3 can achieve an anti-tumor effect through different pathways involving kinase HRI ultimately leading to ATF4/CHOP activation and tumor cell death.
- | Givlaari (givosiran) / Alnylam
Journal: Renal Function Decline With Small Interfering RNA Silencing Aminolevulinic Acid Synthase 1 (ALAS1). (Pubmed Central) - Jul 27, 2021
A long-term deleterious impact of ALAS1 inhibition on renal function is not excluded. Because AIP promotes chronic kidney disease, it is difficult to separate the long-term effects of givosiran from the natural progression of the renal disease.
- | Preclinical, Journal: Inhibition of ALAS1 activity exerts anti-tumour effects on colorectal cancer in vitro. (Pubmed Central) - Feb 20, 2021
The proliferation and metastasis of CRC cells could be inhibited by suppressing ALAS1. The abnormal expression of ALAS1 is closely related to the proliferation and metastasis of CRC cells, suggesting that ALAS1 may be a novel therapeutic target for the treatment of CRC.
- ||| Givlaari (givosiran) / Alnylam
P3 data, Clinical Trial,Phase III, Journal: Phase 3 Trial of RNAi Therapeutic Givosiran for Acute Intermittent Porphyria. (Pubmed Central) - Jun 28, 2020
P3
The increased efficacy was accompanied by a higher frequency of hepatic and renal adverse events. (Funded by Alnylam Pharmaceuticals; ENVISION ClinicalTrials.gov number, NCT03338816.).
- | doxorubicin hydrochloride / Generic mfg.
Journal: Role of aminolevulinic acid synthase 1 in doxorubicin-induced oxidative stress to the ardiomyocyte. (Pubmed Central) - Jan 10, 2020
Inhibition of ALAS1 by ALAS1 siRNA decreased heme and mitochondrial superoxide levels, results in inhibition of doxorubicin-induced apoptosis. ALAS1 plays a pivotal role in the doxorubicin-induced oxidative stress and apoptosis in H9c2 cardiac myocytes.