Geldanamycin / AntiBio Cancer Research Results

Geld, Geldanamycin: Click to Expand ⟱
Features: HSP90 inhibitor

Geldanamycin is a benzoquinone ansamycin antibiotic and natural-product HSP90 inhibitor originally isolated from Streptomyces hygroscopicus. It binds the N-terminal ATP-binding pocket of HSP90, suppressing its chaperone activity and promoting degradation of multiple HSP90 client proteins involved in cancer-cell survival, proliferation, and signalling. Reported downstream effects include inhibition of AKT, RAF/MEK/ERK, receptor tyrosine kinase, and steroid-receptor signalling, with induction of cell-cycle arrest and apoptosis in susceptible cancer cells. The parent compound is primarily a research tool because hepatotoxicity and other toxicities limited clinical development. Geldanamycin has derivatives, including 17-AAG/tanespimycin and 17-DMAG/alvespimycin. Reference.

Geldanamycin — a naturally occurring benzoquinone ansamycin antibiotic and first-generation heat-shock protein 90 inhibitor originally isolated from Streptomyces hygroscopicus. It is formally classified as an experimental natural-product HSP90 chaperone inhibitor and is commonly abbreviated GA or GDM. Geldanamycin competitively occupies the N-terminal ATP-binding pocket of HSP90, disrupting its ATPase-dependent chaperone cycle and destabilizing multiple oncogenic client proteins. The parent compound is used primarily as a research tool; poor aqueous solubility, reactive benzoquinone chemistry, and substantial hepatotoxicity prevented direct clinical development. Semisynthetic analogues include 17-AAG or tanespimycin and 17-DMAG or alvespimycin.

Primary mechanisms (ranked):

  1. N-terminal HSP90 ATPase inhibition, producing prolonged disruption of the HSP90 chaperone cycle.
  2. Ubiquitin-proteasome-dependent depletion of HSP90 client proteins, including context-dependent loss of HER2, EGFR, AKT, RAF, BCR-ABL, SRC, steroid receptors, mutant p53, and cell-cycle regulatory kinases.
  3. Simultaneous suppression of multiple oncogenic survival and proliferation networks, particularly PI3K/AKT, RAF/MEK/ERK, receptor tyrosine kinase, and hormone-receptor signalling.
  4. Induction of cell-cycle arrest and mitochondrial or caspase-dependent apoptosis after client-protein depletion.
  5. Inhibition of hypoxia and angiogenic signalling through destabilization of HIF-1α and associated reduction of VEGF signalling in responsive models.
  6. Radiosensitization and context-dependent chemosensitization through depletion of EGFR, HER2, AKT, DNA-damage-response, and anti-apoptotic proteins.
  7. Secondary activation of HSF1 and induction of HSP70 and other heat-shock proteins, creating a compensatory cytoprotective response that can restrict antitumour efficacy.
  8. Secondary quinone-dependent oxidative stress, which may contribute both to tumour-cell injury and to dose-limiting hepatotoxicity.

Bioavailability / PK relevance: Geldanamycin has poor aqueous solubility, formulation limitations, extensive tissue and hepatic exposure concerns, and a narrow preclinical therapeutic window. Its time-dependent, slow-dissociating interaction with HSP90 can produce prolonged target engagement despite extracellular drug removal. The parent compound has no validated clinical dose or established human pharmacokinetic regimen. More soluble derivatives were developed to improve administration and systemic exposure, but retained variable hepatic and gastrointestinal toxicity.

In-vitro vs systemic exposure relevance: Antiproliferative effects are commonly reported at low-nanomolar to submicromolar concentrations, while biochemical affinity estimates depend strongly on assay conditions, redox state, incubation time, and HSP90 conformation. Continuous or prolonged experimental exposure can exaggerate effects relative to feasible systemic administration. Parent-geldanamycin concentrations producing broad client-protein depletion cannot be assumed clinically achievable because the compound was not advanced into therapeutic human dosing.

Clinical evidence status: Preclinical research agent. Geldanamycin itself has no established therapeutic role, regulatory approval, or demonstrated clinical anticancer efficacy. Its derivatives 17-AAG and 17-DMAG entered phase I and phase II oncology studies and demonstrated pharmacodynamic HSP90 inhibition, but development was constrained by formulation, hepatic, gastrointestinal, ocular, and other toxicities and by limited durable efficacy. Geldanamycin should not be categorized as an approved chemotherapy or clinically validated adjunct.

Mechanistic Effects of Geldanamycin

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 HSP90 chaperone cycle HSP90 ATPase activity ↓ HSP90 ATPase activity ↓ P/R Blocks ATP-dependent client-protein maturation Direct molecular mechanism; binds the N-terminal nucleotide-binding pocket with slow, tight, time-dependent inhibition.
2 HSP90 client-protein stability HER2, EGFR, AKT, RAF, SRC, BCR-ABL and other clients ↓ Physiological HSP90 clients ↓ (dose-dependent) R/G Destabilization and proteasomal degradation of signalling proteins The exact client-protein profile is tumour-type and mutation dependent; loss of several pathways can occur concurrently.
3 PI3K AKT survival signalling AKT and phosphorylated AKT ↓ AKT signalling ↓ (dose-dependent) R/G Reduced survival and treatment resistance Usually secondary to loss of HSP90-dependent AKT stability rather than direct kinase inhibition.
4 RAF MEK ERK signalling RAF stability ↓; ERK signalling ↓ MAPK signalling ↓ (context-dependent) R/G Reduced proliferation and mitogenic signalling Magnitude depends on tumour dependence on RAF and other HSP90 client kinases.
5 Cell-cycle regulation CDK and checkpoint signalling ↓; arrest ↑ Proliferation ↓ (dose-dependent) G G1 or G2/M arrest Phase of arrest varies by cell type and by the client proteins destabilized.
6 Mitochondrial apoptosis Mitochondrial dysfunction ↑; caspase-9 and caspase-3 cleavage ↑; PARP cleavage ↑ Apoptosis ↑ at toxic exposure G Programmed cell death Generally follows depletion of survival clients and is not uniformly induced in all tumour models.
7 HIF-1α and angiogenic signalling HIF-1α stability ↓; VEGF signalling ↓ Hypoxic adaptation ↓ (context-dependent) R/G Reduced hypoxia tolerance and angiogenic signalling HIF-1α is HSP90 dependent, but the magnitude of inhibition varies with oxygen status and tumour model.
8 Radiosensitization Radiation sensitivity ↑ Radiation sensitivity ↔ or ↑ (model-dependent) G Reduced clonogenic survival after irradiation Associated with depletion of EGFR, HER2, AKT, and other stress-response proteins; demonstrated preclinically rather than clinically.
9 Chemosensitization Drug sensitivity ↑ (context-dependent) Treatment toxicity ↑ (possible) G Reduced compensatory survival signalling Combination effects are drug- and tumour-specific and may be limited by overlapping systemic toxicity.
10 HSF1 heat-shock response HSF1 activity ↑; HSP70 and stress proteins ↑ HSF1 activity ↑; cytoprotection ↑ R/G Compensatory proteotoxic-stress response Potential resistance mechanism that partially opposes apoptosis and may protect both malignant and normal cells.
11 Quinone-dependent ROS ROS ↑ (dose-dependent) Hepatic ROS ↑; oxidative injury ↑ P/R Oxidative stress and cellular injury Secondary mechanism rather than the defining anticancer action; particularly important to hepatotoxicity of the benzoquinone scaffold.
12 Clinical Translation Constraint Broad pathway suppression but uncertain therapeutic window Hepatotoxicity and systemic proteostasis disruption ↑ G Prevents clinical use of the parent compound Poor solubility, formulation difficulty, reactive quinone metabolism, normal-tissue HSP90 inhibition, and absent human efficacy data limit translation.

P: 0–30 min    R: 30 min–3 hr    G: >3 hr
AntiBio, Antibiotic/Antimicrobial activity: Click to Expand ⟱
Source:
Type:

Antibiotic / antimicrobial activity: The ability of a substance to suppress or kill microorganisms, especially bacteria, by disrupting microbial survival, growth, biofilm formation, cell-wall integrity, membrane function, protein synthesis, nucleic-acid synthesis, quorum sensing, or virulence.

Natural Products that might have antimicrobial properties

Natural supplement or product Principal constituents Potential antimicrobial activity Evidence assessment Reference
Garlic
Allium sativum		 Allicin, ajoene and diallyl sulfides Antibacterial and antifungal activity, with some antiviral and antiparasitic effects reported in laboratory studies. Extensive laboratory evidence, but insufficient clinical evidence to use garlic as a treatment for established infections. Tesfaye A. Revealing the therapeutic uses of garlic and its potential for drug discovery. Scientific review.
Berberine Berberine isoquinoline alkaloid May damage bacterial membranes, inhibit efflux pumps, interfere with nucleic-acid and protein synthesis, and inhibit biofilm formation. Strong preclinical evidence and limited indication-specific clinical evidence. Poor oral bioavailability and drug interactions limit its use as a general antimicrobial. Berberine as a therapeutic alkaloid against ESKAPE and multidrug-resistant bacteria: a comprehensive review.
Cranberry extract
Vaccinium macrocarpon		 A-type proanthocyanidins Primarily reduces adhesion of uropathogenic bacteria, particularly Escherichia coli, to urinary epithelial cells. May reduce recurrent urinary tract infections in selected populations. It is preventive rather than a reliable treatment for an active UTI. National Center for Complementary and Integrative Health: Cranberry—Usefulness and Safety.
Probiotics
Lactobacillus, Bifidobacterium and Saccharomyces boulardii 		Live microorganisms; effects are strain-specific Competitive exclusion of pathogens, production of bacteriocins, inhibition of pathogen adhesion and restoration of microbiome function. Some human evidence for antibiotic-associated diarrhea and selected gastrointestinal or vaginal indications. Results cannot be generalized from one strain to another. NIH Office of Dietary Supplements: Probiotics—Health Professional Fact Sheet.
Medical-grade honey / Manuka honey Methylglyoxal, hydrogen peroxide, defensin-1, organic acids and high osmolarity Broad topical antibacterial and antibiofilm activity; also supports autolytic debridement and wound healing. Clinically relevant primarily as a standardized, medical-grade topical wound product. Ordinary food honey is not equivalent. Jull AB et al. Honey as a topical treatment for wounds. Cochrane systematic review.
Oregano oil
Origanum vulgare		 Carvacrol and thymol Antibacterial, antifungal and antibiofilm activity, largely through disruption of microbial membranes. Strong laboratory activity, but inadequate human evidence for oral treatment of infections. Concentrated oil can cause irritation. Chemical composition, biological activity and potential uses of oregano and oregano essential oil: a review.
Thyme
Thymus vulgaris		 Thymol and carvacrol Antibacterial, antifungal and antibiofilm activity through membrane damage and altered microbial permeability. Better established as a constituent of topical antiseptic and oral-care formulations than as an oral treatment for systemic infection. PubMed literature: thyme, thymol and antimicrobial activity.
Tea tree oil
Melaleuca alternifolia		 Terpinen-4-ol and related monoterpenes Topical antibacterial and antifungal activity with some antiviral laboratory activity. Some clinical evidence for topical acne and fungal skin conditions. Tea tree oil is toxic when swallowed and may cause contact dermatitis. Carson CF et al. Melaleuca alternifolia oil: a review of antimicrobial and other medicinal properties.
Echinacea
Echinacea species		 Alkamides, caffeic-acid derivatives, polysaccharides and glycoproteins Primarily immunomodulatory; relatively weak and inconsistent direct antimicrobial activity. Evidence for preventing or shortening respiratory infections is inconsistent and preparation-dependent. National Center for Complementary and Integrative Health: Echinacea—Usefulness and Safety.
Elderberry
Sambucus nigra		 Anthocyanins, flavonols and phenolic acids Antiviral effects have been reported in cell-culture and preclinical studies, including interference with viral entry or replication. Small human trials have examined respiratory symptoms, but evidence remains insufficient to establish treatment of influenza or other viral infections. National Center for Complementary and Integrative Health: Elderberry.
Curcumin / turmeric
Curcuma longa		 Curcumin and related curcuminoids Antibacterial, antifungal, antiviral and antibiofilm activity through multiple membrane, enzyme and signalling effects. Predominantly laboratory evidence. Poor aqueous solubility and low systemic bioavailability are major clinical limitations. Moghadamtousi SZ et al. A review on antibacterial, antiviral and antifungal activity of curcumin.
Ginger
Zingiber officinale		 Gingerols, shogaols and zingerone Antibacterial and antifungal activity, including possible inhibition of microbial adhesion and biofilm formation. Primarily laboratory evidence; there is little direct clinical evidence that ginger supplements treat infections. PubMed literature: ginger, gingerols and antimicrobial activity.
Clove
Syzygium aromaticum		 Eugenol and eugenyl acetate Antibacterial, antifungal and local antiseptic activity, principally through membrane and protein disruption. Relevant mainly to topical, food-preservation and dental applications. Evidence for systemic infection treatment is insufficient. PubMed literature: clove, eugenol and antimicrobial activity.
Cinnamon
Cinnamomum species		 Cinnamaldehyde, eugenol and cinnamic acid derivatives Antibacterial, antifungal and antibiofilm activity; may alter microbial membranes and quorum-sensing pathways. Predominantly laboratory evidence. Cassia cinnamon can contribute substantial coumarin exposure when consumed in concentrated amounts. PubMed literature: cinnamon, cinnamaldehyde and antimicrobial activity.
Neem
Azadirachta indica		 Nimbidin, nimbin, nimbolide, azadirachtin and other limonoids Antibacterial, antifungal, antiparasitic and antibiofilm effects have been reported. Some topical and dental research exists, but systemic clinical evidence is inadequate. Oral neem preparations have important safety concerns. PubMed literature: Azadirachta indica and antimicrobial activity.
Black seed
Nigella sativa		 Thymoquinone, thymohydroquinone and related volatile compounds Antibacterial, antifungal, antiparasitic and possible antiviral activity. Considerable laboratory research but limited, heterogeneous clinical evidence for infectious diseases. PubMed literature: Nigella sativa, thymoquinone and antimicrobial activity.
Green tea extract
Camellia sinensis		 Epigallocatechin gallate (EGCG) and other catechins Antibacterial, antiviral and antibiofilm activity; may damage membranes, inhibit microbial enzymes and enhance some antibiotics. Some localized oral-health evidence, but limited evidence for treating systemic infections. Concentrated extracts may cause liver injury in susceptible individuals. PubMed literature: EGCG, green tea and antimicrobial activity.
Licorice root
Glycyrrhiza species		 Glycyrrhizin, glycyrrhetinic acid, liquiritigenin and other flavonoids Antiviral, antibacterial and antifungal effects have been reported in laboratory and preclinical studies. Limited clinical antimicrobial evidence. Glycyrrhizin can cause hypertension, hypokalemia, fluid retention and clinically important drug interactions. National Center for Complementary and Integrative Health: Licorice Root.
Andrographis
Andrographis paniculata		 Andrographolide and related diterpenoid lactones Immunomodulatory, anti-inflammatory and possible antiviral or antibacterial activity. Some evidence for modest symptom reduction in uncomplicated respiratory infections, but this does not establish direct pathogen eradication. PubMed literature: Andrographis and respiratory infections.
Pelargonium sidoides Proanthocyanidins, phenolic acids and oxygenated coumarin derivatives Possible antiviral, antibacterial anti-adhesive and immunomodulatory activity. Some human evidence for modest symptom improvement in acute bronchitis and selected respiratory infections. It is not a substitute for antibiotics when bacterial treatment is indicated. Timmer A et al. Pelargonium sidoides extract for acute respiratory tract infections. Cochrane systematic review.
Monolaurin
Glycerol monolaurate		 Monolaurin, a monoester derived from lauric acid May disrupt lipid membranes and interfere with signalling or virulence in certain bacteria and enveloped viruses. Predominantly laboratory and animal evidence. There is insufficient clinical evidence to recommend oral monolaurin for infections. PubMed literature: glycerol monolaurate and antimicrobial activity.
Caprylic acid Octanoic acid, an eight-carbon medium-chain fatty acid Antifungal and membrane-disrupting activity, particularly against Candida species, has been reported in vitro. Insufficient human evidence for treating candidiasis or systemic fungal infection. Marketing claims commonly exceed the evidence. PubMed literature: caprylic acid and Candida.
Olive leaf extract
Olea europaea		 Oleuropein, hydroxytyrosol and elenolic-acid derivatives Antibacterial, antiviral and antifungal activity has been observed in laboratory studies. Preliminary evidence only; clinical trials have not established it as a treatment for infectious disease. PubMed literature: olive leaf, oleuropein and antimicrobial activity.
Goldenseal
Hydrastis canadensis		 Hydrastine, canadine and berberine Extracts and individual alkaloids show antibacterial activity in laboratory studies. There is no good clinical evidence that goldenseal treats human infections. Product composition, absorption and drug interactions are important limitations. National Center for Complementary and Integrative Health: Goldenseal.
Sweet wormwood / artemisinin
Artemisia annua 		Artemisinin and related sesquiterpene lactones Artemisinin derivatives are potent antimalarial agents. Additional antibacterial, antiviral and antiparasitic effects are being studied. Artemisinin-based combination therapies are established medicines, not ordinary supplements. Herbal preparations should not replace standardized malaria treatment because dose variability can promote treatment failure and resistance. World Health Organization: Guidelines for malaria.

Evidence interpretation

  • Clinical evidence: Effects have been studied in human participants, but usually for a specific preparation, route, dose and indication.
  • Preclinical evidence: Activity has mainly been demonstrated in cell culture, microbial cultures or animal models.
  • Anti-adhesive or probiotic activity: The product may reduce colonization or pathogen attachment without directly killing the microorganism.
  • Topical evidence: Results from topical use cannot be assumed to apply to an orally administered supplement.


Scientific Papers found: Click to Expand⟱
7101- Geld,    Reactive oxygen species mediate hepatotoxicity induced by the Hsp90 inhibitor geldanamycin and its analogs
- in-vitro, Nor, NA
*toxicity↑, *AntiBio↑, HSP90↓, AntiCan↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Protein Folding & ER Stress(tgid=8) ⓘ

HSP90↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,  
Total Targets: 2

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

AntiBio↑, 1,  

Functional Outcomes(tgid=23) ⓘ

toxicity↑, 1,  
Total Targets: 2

Scientific Paper Hit Count for: AntiBio, Antibiotic/Antimicrobial activity
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:422  Target#:1483  State#:%  Dir#:%
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