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SDH-deficient disease drug repurposing overview

Drug Candidates
15

Across 7 pathways

Pathways Mapped
7

Druggable downstream pathways

Molecular Targets
16

Identified drug targets

AI Hypotheses
0

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SDH Deficiency Molecular Cascade

From mutation to druggable pathways — click a pathway to see targeting drugs

MUTATION

SDH Loss (SDHA/B/C/D/AF2)

PRIMARY EVENT

Succinate Accumulation

Oncometabolite (> 100x normal levels)

MECHANISM

Inhibits α-KG-dependent dioxygenases

PHDs, TETs, KDMs, and other 2-oxoglutarate enzymes

DOWNSTREAM DRUGGABLE PATHWAYS

HIF

Pseudohypoxia / HIF Pathway

3 drugs targeting

Epigenetic

Epigenetic Dysregulation

5 drugs targeting

VEGF

VEGF Signaling

3 drugs targeting

mTOR

mTOR / PI3K / AKT

3 drugs targeting

Glutamine

Glutamine Dependency

1 drug targeting

ROS

Oxidative Stress / ROS

3 drugs targeting

Autophagy

Autophagy / Survival

0 drugs targeting

Top Drug Candidates by Evidence Score

Belzutifan

Welireg

established

HIF-2α inhibitor

Hif Pseudohypoxia
Evidence Score
82
FDA Approved
Sunitinib

Sutent

established

Multi-kinase inhibitor (VEGFR/PDGFR/KIT)

Vegf SignalingMtor Pi3k Akt
Evidence Score
75
FDA Approved
Temozolomide

Temodar, Temodal

clinical trial

Alkylating agent

Epigenetic Dysregulation
Evidence Score
68
FDA Approved
Bevacizumab

Avastin

established

Anti-VEGF monoclonal antibody

Vegf Signaling
Evidence Score
65
FDA Approved
Telaglenastat

CB-839

clinical trial

Glutaminase inhibitor

Glutamine Dependency
Evidence Score
60
Regorafenib

Stivarga

established

Multi-kinase inhibitor (VEGFR/KIT/PDGFR/FGFR/RAF)

Vegf SignalingMtor Pi3k Akt
Evidence Score
58
FDA Approved