Delving into the Latest Updates on Luminespib with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Luminespib (USAN/INN), Luminespib Mesylate

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Target

HSP90

Mechanism

HSP90 inhibitors(Heat shock 90kDa proteins inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Head and Neck Neoplasms

Inactive Indication

Adenocarcinoma of LungAdvanced gastric carcinomaAdvanced HER2-Positive Breast Carcinoma+ [25]

Originator Organization

Ligand UK Ltd.

Active Organization

The Institute of Cancer Research: Royal Cancer Hospital

Inactive Organization

Novartis Pharmaceuticals Corp.

Beijing Novartis Pharma Co. Ltd.

Novartis AG

+ [1]

Drug Highest PhasePhase 2

First Approval Date-

RegulationSpecial Review Project (CN)

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Structure

Molecular FormulaC26H31N3O5

InChIKeyNDAZATDQFDPQBD-UHFFFAOYSA-N

CAS Registry747412-49-3

This phase I trial studies the side effects and the best dose of Hsp90 inhibitor AUY922 when given together with pemetrexed disodium in treating patients with previously treated stage IV non-small cell lung cancer. Hsp90 inhibitor AUY922 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop the growth of tumor cell, either by killing the cells or stopping them from dividing. Giving Hsp90 inhibitor AUY922 together with pemetrexed disodium may kill more tumor cells

Start Date31 Jan 2014

Sponsor / Collaborator

Jonsson Comprehensive Cancer Center

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100 Clinical Results associated with Luminespib

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100 Translational Medicine associated with Luminespib

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100 Patents (Medical) associated with Luminespib

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244

Literatures (Medical) associated with Luminespib

01 Nov 2024·European Journal of Medicinal Chemistry

HSP90/LSD1 dual inhibitors against prostate cancer as well as patient-derived colorectal organoids

Article

Author: Liou, Jing-Ping ; Cheng, Li-Hsin ; Chen, I-Chung ; Cho, Er-Chieh ; Tsai, Kelvin K. ; Chen, Mei-Chuan ; Zhao, Jian-Xun ; Lin, Tony Eight ; Tang, Di-Wei ; Lai, Mei-Jung ; Chou, Po-Yu ; Hsu, Kai-Cheng ; Chang, Hung-Hsuan ; Liu, Zheng-Yang ; Tsai, Kelvin K

The rational installation of pharmacophores targeting HSP90 and LSD1 axes has achieved significant anti-cancer capacity in prostate and colorectal cancer. Among the series of hybrids, inhibitor 6 exhibited remarkable anti-proliferative activity against prostate cancer cell lines PC-3 and DU145, with GI₅₀ values of 0.24 and 0.30 μM, respectively. It demonstrated notable efficacy in combinatorial attack and cell death initiation towards apoptosis. The cell death process was mediated by PARP induction and γH2AX signaling, and was also characterized as caspase-dependent and Bcl-xL/Bax-independent. Notably, no difference in eye size or morphology was observed in the zebrafish treated with compound 6 compared to the reference group (AUY922). The profound treatment response in docetaxel-resistant PC-3 cells highlighted the dual inhibitory ability in improving docetaxel sensitivity. Additionally, at a minimum concentration of 1.25 μM, compound 6 effectively inhibited the growth of patient-derived colorectal cancer (CRC) organoids for up to 10 days in vitro. Together, the designed HSP90/LSD1 inhibitors present a novel route and significant clinical value for anti-cancer drug therapy.

08 Aug 2024·Journal of Medicinal Chemistry

New Class of Hsp90 C-Terminal Domain Inhibitors with Anti-tumor Properties against Triple-Negative Breast Cancer

Article

Author: Zubrienė, Asta ; Ogris, Iza ; Gedgaudas, Marius ; Mitrović, Ana ; Zajec, Živa ; Cingl, Jernej ; Gobec, Martina ; Golič Grdadolnik, Simona ; Dernovšek, Jaka ; Tomašič, Tihomir

Triple-negative breast cancer (TNBC) remains a treatment challenge and requires innovative therapies. Hsp90, crucial for the stability of numerous oncogenic proteins, has emerged as a promising therapeutic target. In this study, we present the optimization of the Hsp90 C-terminal domain (CTD) inhibitor TVS21. Biochemical methods, NMR binding studies, and molecular modeling were employed to investigate the binding of representative analogs to Hsp90. The newly synthesized analogs showed increased antiproliferative activity in breast cancer cell lines, including the MDA-MB-231 TNBC cell line. Compounds 89 and 104 proved to be the most effective, inducing apoptosis, slowing proliferation, and degrading key oncogenic proteins without inducing a heat shock response. In vivo, compound 89 showed comparable efficacy to the clinical candidate AUY922 and a better safety profile in a TNBC xenograft model. These results highlight the promise of Hsp90 CTD inhibitors for TNBC therapy, potentially filling a significant treatment gap.

01 Jul 2024·Heliyon

AUY922 improves sensitivity to sunitinib in clear cell renal cell carcinoma based on network pharmacology and in vitro experiments

Article

Author: Jia, Xing ; Cheng, Sheng ; Liu, Min ; Song, Ya ; Cai, Yuesong ; Chen, Zixuan ; Tong, Yanjun

Clear Cell Renal Cell Carcinoma (ccRCC), the most prevalent form of renal cell carcinoma (RCC), poses a significant threat to human health due to its rising morbidity and mortality rates. Sunitinib, a pivotal targeted drug for the treatment of ccRCC, presents a significant challenge due to the high susceptibility of ccRCC to resistance. HSP90 inhibitor AUY922 has demonstrated anti-tumor activity in a range of cancer types. However, its efficacy in combination with sunitinib for ccRCC treatment has not been evaluated. In this study, we employed bioinformatics, network pharmacology, and in vitro assays to verify that AUY922 inhibits cell viability, proliferation, and migration of ccRCC cell lines 786-O and ACHN, with IC50s of 91.86 μM for 786-O and 115.5 μM for ACHN. The effect of AUY922 enhancing the inhibitory effect of sunitinib on ccRCC was further confirmed. The CCK-8 assay demonstrated that the IC50 of sunitinib was reduced from 15.10 μM to 11.91 μM for 786-O and from 17.65 μM to 13.66 μM for ACHN, after the combined application of AUY922. The EdU assay and wound healing assay indicated that AUY922 augmented the inhibitory impact of sunitinib on the proliferation and migration of ccRCC cells. Western blot and RT-PCR analyses demonstrated that AUY922 increased the sensitivity of ccRCC cells to sunitinib by targeting the HIF-1α/VEGFA/VEGFR pathway. Our study represents the first investigation into the role and mechanism of AUY922 in enhancing the sensitivity of ccRCC to sunitinib. In conclusion, the findings indicate the potential for AUY922 to enhance the therapeutic efficacy of sunitinib and overcome sunitinib resistance in ccRCC.

100 Deals associated with Luminespib

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External Link

KEGG	Wiki	ATC	Drug Bank
D10646	Luminespib	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Discovery	US	Novartis Pharmaceuticals Corp.	01 Jul 2007
Advanced Malignant Solid Neoplasm	Discovery	GB	Novartis Pharmaceuticals Corp.	01 Jul 2007
Advanced Malignant Solid Neoplasm	Discovery	NL	Novartis Pharmaceuticals Corp.	01 Jul 2007
Advanced Malignant Solid Neoplasm	Discovery	CH	Novartis Pharmaceuticals Corp.	01 Jul 2007
Hematologic Neoplasms	Discovery	GB	Novartis Pharmaceuticals Corp.	01 Jul 2007
Hematologic Neoplasms	Discovery	NL	Novartis Pharmaceuticals Corp.	01 Jul 2007
Hematologic Neoplasms	Discovery	CH	Novartis Pharmaceuticals Corp.	01 Jul 2007
Metastatic human epidermal growth factor 2 positive carcinoma of breast	Discovery	NL	Novartis Pharmaceuticals Corp.	01 Jul 2007
Metastatic human epidermal growth factor 2 positive carcinoma of breast	Discovery	GB	Novartis Pharmaceuticals Corp.	01 Jul 2007
Metastatic human epidermal growth factor 2 positive carcinoma of breast	Discovery	US	Novartis Pharmaceuticals Corp.	01 Jul 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01259089 (CTgov)	Phase 1/2	Non-small cell lung cancer stage IIIB	38	needle biopsy+erlotinib hydrochloride+Hsp90 inhibitor AUY922	psduqeocdo(pszalfoamv) = vzujtlmnix jdavhcwloe (uuasqwjudn, lowsuxufxb - hflrntbwis) View more	-	21 Nov 2018
NCT01854034 (Pubmed \| Ann Oncol)	Phase 2	EGFR ex20ins mutation in non-small cell lung cancer	29	Luminespib	(ortfvzxfbd) = esthofbhwm ckksosccwt (jxvuukgwch ) View more	Positive	01 Oct 2018
WCLC2018	Not Applicable	Metastatic Non-Squamous Non-Small Cell Lung Carcinoma	13	AUY922	ggwmkjptix(odszpvchoj) = Tolerability of AUY922 with pemetrexed is limited by ocular toxicity dmibkcmups (jovvuiznml ) View more	-	25 Sep 2018
NCT01854034 (CTgov)	Phase 2	Non-Small Cell Lung Cancer	29	AUY922	noufhiioud(dmbgjwetut) = snqriktmse zonfxmborb (kylfmonnja, rangzszlfe - udbnukloww) View more	-	10 Apr 2018
NCT01124864 (Pubmed \| J Thorac Oncol)	Phase 2	Advanced Lung Non-Small Cell Carcinoma	153	AUY922	(bpxugosulm) = 35 patients (22.9%) reported night blindness zeojrpqbfe (oorsoyoetd ) View more	-	01 Apr 2018
NCT01752400 (CTgov)	Phase 2	ALK positive Lung Cancer \| ALK positive Non-Small Cell Lung Cancer	6	AUY922	ipqtglehnj(ojgcebdnon) = upaglsmcvu wyyhmexxch (xyxhoqmnhj, xhiwagxvjp - gttrueplip) View more	-	29 Mar 2018
NCT01854034 (WCLC2017)	Phase 2	Non-Small Cell Lung Cancer	29	Luminespib (AUY922)	(uoffnpfewh) = xwzhzzyqfw apcivvnbys (hvnkmwddzo ) View more	Positive	18 Oct 2017
NCT01646125 (CTgov)	Phase 2	Advanced Lung Non-Small Cell Carcinoma	59	AUY922 (AUY922 Arm)	niidevcpsd(djjacjocli) = gusjuqxhhq bupouyzjsi (sjqeykiihr, tyesyfbddv - gfdbwymtqn) View more	-	13 Mar 2017
NCT01646125 (CTgov)	Phase 2	Advanced Lung Non-Small Cell Carcinoma	59	docetaxel+pemetrexed (Chemotherapy Arm)	niidevcpsd(djjacjocli) = wiiphatwjn bupouyzjsi (sjqeykiihr, gxwxjndnue - rvsuytcbra) View more	-	13 Mar 2017
NCT01485536 (CTgov)	Phase 2	Lymphoma	21	AUY922	qyuikjycke(kulezjfwci) = tmstvzcnyk xsedysqazy (mhfrbxgqei, wvejgmhygs - lcdxgvtkgv) View more	-	23 Jan 2017
NCT01404650 (CTgov)	Phase 2	Gastrointestinal Stromal Tumors	25	AUY922	(gygngrksdu) = ctjrsqhczx soytsxthcd (orsqkdsrcf, zxthpywiek - ifzuvmgftv) View more	-	04 Oct 2016