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DRUG:

BOLD-100

i
Other names: BOLD-100, IT-139, NKP-1339, BOLD 100, KP-1339, BOLD100
Associations
Company:
Bold Therap, Hana Pharm
Drug class:
Reactive oxygen species stimulant, GRP78 inhibitor
Associations
3ms
BOLD-100-001: BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours (clinicaltrials.gov)
P1/2, N=220, Recruiting, Bold Therapeutics, Inc. | Active, not recruiting --> Recruiting | Phase classification: P1b/2a --> P1/2 | N=117 --> 220 | Trial completion date: Sep 2024 --> Sep 2026 | Trial primary completion date: Dec 2023 --> Jun 2026
Enrollment open • Phase classification • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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5-fluorouracil • leucovorin calcium • BOLD-100
4ms
Ruthenium drug BOLD-100 regulates BRAFMT colorectal cancer cell apoptosis through AhR/ROS/ATR signaling axis modulation. (PubMed, Mol Cancer Res)
These results unveil possible novel therapeutic opportunity for BRAFMT CRC. Implications: BOLD-100 induces BRAFMT-dependent replication stress, and targeted strategies against replication stress (eg. by using ATR inhibitors) in combination with BOLD-100 may serve as a potential novel therapeutic strategy for clinically aggressive BRAFMT CRC.
Journal
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CHEK1 (Checkpoint kinase 1) • CYP1A1 (Cytochrome P450 Family 1 Subfamily A Member 1)
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BOLD-100
5ms
Coumarin-modified ruthenium complexes: Synthesis, characterization, and antiproliferative activity against human cancer cells. (PubMed, Arch Pharm (Weinheim))
Among ruthenium complexes studied as anticancer metallodrugs, NKP-1339, NAMI-A, RM175, and RAPTA-C have already entered clinical trials due to their potent antitumor activity demonstrated in preclinical studies and reduced toxicity in comparison with platinum drugs...Coumarin derivative 2a positively regulated the expression and activity of c-Myc and NPM1 in RKO colon carcinoma cells, while the Ru(II) half-sandwich complex 2cRu induced downregulation of AKT and ERK signaling in PANC-1 cells concomitant with reduced intracellular levels of reactive oxygen species. Altogether, our findings indicated that coumarin-modified half-sandwich Ru(II) complexes held potential as anticancer agents against gastrointestinal malignancies.
Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • NPM1 (Nucleophosmin 1)
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BOLD-100
1year
The Lipid Metabolism as Target and Modulator of BOLD-100 Anticancer Activity: Crosstalk with Histone Acetylation. (PubMed, Adv Sci (Weinh))
Summarizing, BOLD-100 is identified as epigenetically active substance acting via targeting several onco-metabolic pathways. Identification of the lipid metabolism as driver of acquired BOLD-100 resistance opens novel strategies to tackle therapy failure.
Journal • Epigenetic controller
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SLC16A1 (Solute Carrier Family 16 Member 1) • BSG (Basigin (Ok Blood Group))
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BOLD-100
1year
BOLD-100-001: BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours (clinicaltrials.gov)
P1b/2a, N=117, Active, not recruiting, Bold Therapeutics, Inc. | Recruiting --> Active, not recruiting
Enrollment closed • Combination therapy • Metastases
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HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5)
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5-fluorouracil • leucovorin calcium • BOLD-100
over1year
The Metallodrug BOLD-100 Is a Potent Inhibitor of SARS-CoV-2 Replication and Has Broad-Acting Antiviral Activity. (PubMed, Biomolecules)
In addition, we showed that the antiviral activity of BOLD-100 is not specific for SARS-CoV-2, but also inhibits the replication of the evolutionarily divergent viruses Human Immunodeficiency Virus type 1 and Human Adenovirus type 5. This study identifies BOLD-100 as a potentially novel broad-acting antiviral drug.
Journal
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BOLD-100
over1year
Novel metallotherapeutic BOLD-100 induces circulating cytokine changes when administered in combination with FOLFOX in advanced gastrointestinal cancer patients (AACR 2023)
Proven metallotherapeutics, such as cisplatin and oxaliplatin, alter immune responses as part of their multimodal mechanisms-of-action...These results show that BOLD-100 in combination with FOLFOX can induce immune responses, and that these immune responses may predict clinical outcome. Analysis of additional patient samples from the Phase 2 trial is ongoing.
Clinical • Combination therapy • Metastases
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TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • CCL4 (Chemokine (C-C motif) ligand 4) • CCL11 (C-C Motif Chemokine Ligand 11) • IL18 (Interleukin 18) • HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5) • TGFA (Transforming Growth Factor Alpha)
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cisplatin • 5-fluorouracil • oxaliplatin • leucovorin calcium • BOLD-100
almost2years
BOLD-100-001: BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours (clinicaltrials.gov)
P1b/2a, N=100, Recruiting, Bold Therapeutics, Inc. | Trial completion date: Dec 2023 --> Sep 2024 | Trial primary completion date: Dec 2022 --> Dec 2023
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5)
|
5-fluorouracil • leucovorin calcium • BOLD-100
2years
BOLD-100-001: BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours (clinicaltrials.gov)
P1b/2a, N=100, Recruiting, Bold Therapeutics, Inc. | Phase classification: P1b --> P1b/2a | Trial completion date: Jan 2023 --> Dec 2023
Phase classification • Trial completion date • Combination therapy • Metastases
|
HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5)
|
5-fluorouracil • leucovorin calcium • BOLD-100
2years
ER Stress Response and Induction of Apoptosis in Malignant Pleural Mesothelioma: The Achilles Heel Targeted by the Anticancer Ruthenium Drug BOLD-100. (PubMed, Cancers (Basel))
Our studies demonstrated that BOLD-100 increases ROS production and Ca release from the ER, leading to ER stress activation and, ultimately, to cell death. Our in vitro data strongly suggest that BOLD-100 inhibits the growth of MPM cell lines, proposing the application as a single agent, or in combination with other standard-of-care drugs, to treat MPM.
Journal
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HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5)
|
BOLD-100
over2years
BOLD-100-001: BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours (clinicaltrials.gov)
P1b, N=80, Recruiting, Bold Therapeutics, Inc. | Trial completion date: Mar 2022 --> Jan 2023 | Trial primary completion date: Dec 2021 --> Dec 2022
Trial completion date • Trial primary completion date • Combination therapy
|
HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5)
|
5-fluorouracil • leucovorin calcium • BOLD-100
over2years
Utilization of cancer cell line screening and bioinformatic analyses to identify optimal developmental pathways for the novel anticancer agent BOLD-100 (AACR 2022)
Utilizing bladder cancer as a case study, subsequent combination testing of BOLD-100 in combination with fluorouracil or cisplatin demonstrated that BOLD-100 enhanced cell death across different bladder cancer cell lines through synergistic interactions with these standard-of-care agents...Collectively, BOLD-100 showed a unique sensitivity profile across a panel of over 300 cancer cell lines, identifying multiple potential indications for future development. Subsequent investigations into several cancer types of interest and drug combinations are ongoing.
Preclinical
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KRAS (KRAS proto-oncogene GTPase) • HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5)
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KRAS mutation
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cisplatin • 5-fluorouracil • leucovorin calcium • BOLD-100
4years
Inhibition of DNA Repair Pathways and Induction of ROS Are Potential Mechanisms of Action of the Small Molecule Inhibitor BOLD-100 in Breast Cancer. (PubMed, Cancers (Basel))
BOLD-100, a ruthenium-based complex, sodium trans-[tetrachloridobis (1H-indazole) ruthenate (III)] (also known as IT-139, NKP1339 or KP1339), is a novel small molecule drug that demonstrated a manageable safety profile at the maximum tolerated dose and modest antitumor activity in a phase I clinical trial. In estrogen receptor negative (ER-) breast cancer cells, combination of BOLD-100 with a PARP inhibitor, olaparib, induced significant inhibition of cell growth and xenografts and increased gamma-H2AX. Thus, BOLD-100 is a novel DNA repair pathway targeting agent and can be used with other chemotherapies in ER- breast cancer.
Journal • PARP Biomarker
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ER (Estrogen receptor)
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ER positive
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Lynparza (olaparib) • BOLD-100