This is a Phase 1, first-in-human (FIH) clinical study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of IK-930, an oral TEAD inhibitor, administered orally (PO) as monotherapy in subjects with advanced solid tumors with or without gene alterations in the Hippo pathway for whom there are no further treatment options known to confer clinical benefit. The study consists of two phases, an initial Dose Escalation phase followed by a Dose Expansion phase.

开始日期2022-01-07

申办/合作机构

Ikena Oncology, Inc.

100 项与 IK-930 相关的临床结果

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100 项与 IK-930 相关的转化医学

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100 项与 IK-930 相关的专利（医药）

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项与 IK-930 相关的文献（医药）

2023-12-31·Journal of enzyme inhibition and medicinal chemistry

Discovery of 3-((3-amino- 1H -indazol-4-yl)ethynyl)- N -(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide (AKE-72), a potent Pan-BCR-ABL inhibitor including the T315I gatekeeper resistant mutant

Article

作者: Nam, Yunju ; Park, Jung Woo ; Keum, Gyochang ; El-Damasy, Ashraf K ; Kim, Hyun Ji ; Hur, Wooyoung ; Bang, Eun-Kyoung

BCR-ABL inhibition is an effective therapeutic approach for the treatment of chronic myeloid leukaemia (CML). Herein, we report the discovery of AKE-72 (5), a diarylamide 3-aminoindazole, as a potent pan-BCR-ABL inhibitor, including the imatinib-resistant mutant T315I. A focussed array of compounds 4a, 4b, and 5 has been designed based on our previously reported indazole I to improve its BCR-ABL^T315I inhibitory activity. Replacing the morpholine moiety of I with the privileged tail (4-ethylpiperazin-1-yl)methyl afforded 5 (AKE-72) with IC₅₀ values of < 0.5 nM, and 9 nM against BCR-ABL^WT and BCR-ABL^T315I, respectively. Moreover, AKE-72 potently inhibited a panel of other clinically important mutants in single-digit nanomolar IC₅₀ values. AKE-72 elicited remarkable anti-leukemic activity against K-562 cell line (GI₅₀ < 10 nM, TGI = 154 nM). In addition, AKE-72 strongly inhibited the proliferation of Ba/F3 cells expressing native BCR-ABL or its T315I mutant. Overall, AKE-72 may serve as a promising candidate for the treatment of CML, including those harbouring T315I mutation.

2019-06-01·Bioorganic chemistry2区 · 化学

Synthesis, evaluation and docking of novel pyrazolo pyrimidines as potent p38α MAP kinase inhibitors with improved anti-inflammatory, ulcerogenic and TNF-α inhibitory properties

2区 · 化学

Article

作者: Amir, Mohd ; Somakala, Kanagasabai ; Tariq, Sana

A series of nine new N-substituted-4-((1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)amino)benzamides (6a-i) derivatives was synthesized. All the compounds were screened in-vitro for BSA anti-denaturation property, antioxidant assay and p38α MAP kinase inhibition. The in vitro anti-inflammatory assay results revealed that the compounds (6f-i) showed better activity than the compounds 6a-e. Compound 6f bearing the 4-chlorophenyl group showed in vitro anti-inflammatory activity (82.35 ± 4.04) comparable to standard drug diclofenac sodium (84.13 ± 1.63) and better p38α MAP kinase inhibitory activity (IC₅₀ = 0.032 ± 1.63 µM) than the prototypic inhibitor SB203580 (IC₅₀ = 0.041 ± 1.75 µM). The selected active compounds (6f-i) were further studied in animal models for anti-inflammatory activity, ulcerogenic liability, lipid peroxidation and TNF-α inhibition potential. Compound 6f showed promising anti-inflammatory potential with a percentage inhibition of 83.73% when compared to the standard, diclofenac sodium (78.05%). Compound 6f was also found to show reduced ulcerogenic liability and lipid peroxidation in comparison to the standard. This compound also potently inhibited the lipopolysaccharide (LPS)-induced TNF-α production in mice model (ID₅₀ = 8.23 mg/kg) in comparison to SB 203580 (ID₅₀ = 26.38 mg/kg). The molecular docking of compounds 6a-i against p38α MAP kinase receptor was also performed to understand ligand receptor interaction. Amongst all synthesized molecules compound 6f displayed highest docking score of -9.824. It showed hydrogen bonding interactions with Asn115 and pi-cation interaction with Lys53.

2013-09-18·Journal of agricultural and food chemistry1区 · 农林科学

Design, Synthesis, and Insecticidal Evaluation of New Pyrazole Derivatives Containing Imine, Oxime Ether, Oxime Ester, and Dihydroisoxazoline Groups Based on the Inhibitor Binding Pocket of Respiratory Complex I

1区 · 农林科学

Article

作者: Wang, Qingmin ; Yang, Na ; Li, Yongqiang ; Song, Hongjian ; Liu, Yuxiu ; Xiong, Lixia

On the basis of complex I receptor protein binding site and commercial tebufenpyrad and tolfenpyrad, four series of novel pyrazole-5-carboxamides containing imine, oxime ether, oxime ester, and dihydroisoxazoline were designed and synthesized via the key intermediate 4-chloro-3-ethyl-N-(4-formylbenzyl)-1-methyl-1H-pyrazole-5-carboxamide. The structures of target compounds were confirmed by ¹H NMR and high-resolution mass spectrum (HRMS). The results of bioassays indicated that the target compounds possessed good-to-excellent activities against a broad spectrum of insects such as cotton bollworm (Helicoverpa armigera), spider mite (Tetranychus cinnabarinus), bean aphid (Aphis craccivora), and mosquito (Culex pipiens pallens), but gave different structure-activity relationships for each species. Compounds containing imine showed high insecticidal activity against cotton bollworm. Especially, stomach activity of compounds 5-1c was 60% at 11 mg kg⁻¹. The compounds also had good activities against bean aphid and mosquito. The foliar contact activity of compounds 5-1a, 5-1b, 5-1e, 5-3c, and 5-3d against bean aphid were 90, 100, 90, 90, and 90%, respectively, at 200 mg kg⁻¹. The activity of compound containing dihydroisoxazoline moiety (5-4) against mosquito was 60% at 1 mg kg⁻¹, which was near that of tebufenpyrad. The introduction of dihydroisoxazoline structure (5-4) was advantageous to improve the activity of the compound against adult mites compared with other structures; the miticidal activity of 5-4- against adult mites was 60% at 50 mg kg⁻¹.

项与 IK-930 相关的新闻（医药）

2024-05-30

·Pharmaceutical Technology

Ikena further sheds staff and pipeline in bid to maximise value

Ikena will terminate approximately 18 employees, 53% of its workforce, by the end of Q3 this year. Image Credit: Zern Liew / Shutterstock. For the second time this year, US-based Ikena Oncology has announced plans for workforce reduction and pipeline prioritisation. Recommended Buyer's Guides Buyer's Guide Top Guide for Drug Delivery Systems Buyer's Guide Top Guide for Cleanrooms and Cleanroom Flooring The company plans to reduce its workforce by 53% by Q3 this year. The staff layoffs are expected to cost approximately $1.2m. Ikena reported cash reserves of $157m as of 31 March 2024, down $18m from the end of Q4 last year. Ikena has also discontinued developing its selective Hippo pathway inhibitor, IK-930, and will start “winddown activities”. The company added it will seek “strategic options” for the programme, including partnership agreements that could explore the “development of IK-930 in combination with other targeted agents”. In January, Ikena announced cash-saving measures , including a 35% reduction in its workforce and the stoppage of its exploratory research and discovery efforts. At that time, the company had focused on IK-930 as one of the two therapies for further development. See Also: Dupixent gets closer to EU approval as the FDA delays its decision on COPD Bristol Myers Squibb’s Breyanzi gains FDA approval for lymphoma IK-930 is a selective Hippo pathway inhibitor that targets TEA domain transcription factor 1 (TEAD1). The drug was being investigated in a Phase I trial (NCT05228015) in patients with solid tumours. The company planned to focus its development on treating epithelioid haemangioendothelioma (EHE) and mesothelioma. Following the latest round of pipeline reprioritisation, Ikena has one therapy in its pipeline – IK-595, a MEK-RAF molecular glue. It targets the RAS signalling pathway, responsible for cancer cell proliferation. The drug is currently in Phase I trial in patients with RAS and RAF mutant cancers. Early Phase I data with the drug showed an 80% pERK inhibition at four hours post-dosing, with an above 60% inhibition sustained through 24 hours. pERK is one of the major transducers of endoplasmic reticulum stress, participating in regulating fundamental cell functions. Multiple pharmaceutical companies have announced layoffs in recent months amid a difficult economic environment . Last month, Novartis announced plans to lay off approximately 680 staff members . The plans were separate from the company’s overall restructuring programme, which could involve up to 8,000 workers. Xilio Therapeutics also dismissed 21% of its staff in April. Additionally, the company terminated the development of XTX202, a tumour-activated beta-gamma biased interleukin (IL)-2. Similar to Ikena, Xilio did not outright dismiss the development of the therapy but instead stated that it would explore partnerships to develop the therapy as a combination treatment.

临床1期上市批准临床结果财报临床2期

2024-05-29

·FierceBiotech

Ikena cuts Hippo med, half of staff in latest reprioritization

Ikena Oncology is evaluating strategic options for the company and its development pipeline. Ikena Oncology is again shrinking its herd and signaling a tough fight ahead as one of two assets, a TEAD1-selective Hippo pathway inhibitor, is cut. The cancer biotech is laying off more than half of its workforce, which means 18 people, according to a Tuesday regulatory filing. The move comes after January cuts saw 35% of the workforce let go. Ikena expects to incur $1.2 million in expenditures related to the most recent round of layoffs, which will be completed in the third quarter. About 16 employees are expected to remain on staff when all is said and done, according to the filing. At the same time, the company is axing development of IK-930, which is one of two meds Ikena had zeroed in on during the January reprioritization. The therapy had been under development for mesothelioma and epithelioid hemangioendothelioma. Now, Ikena will solely focus on the molecular glue IK-595 for RAS and RAF mutant cancers. A phase 1 trial is currently enrolling, with additional cohorts expected to be added in the second half of this year. Despite all of these dramatic cuts, the company is still not in the clear. Ikena said it is also evaluating strategic options for the company and its development pipeline, which could include an acquisition, merger, asset sale partnership or other transactions, the filing stated. “Ikena is in a strong position to create value through multiple avenues. We have been diligent with our capital expenditure, fortifying a cash position that may unlock new strategic opportunities for the company, in addition to the parallel partnership potential of our pipeline,” said Chief Financial Officer Jotin Marango, M.D., Ph.D., in a Tuesday evening press release. The biotech had $157 million in cash and equivalents as of March 31. William Blair analysts called the reprioritizations a tough decision and the discontinuation of IK-930, particularly, a "disappointment." The therapy had been rejigged after an earlier clinical failure, and William Blair had been expecting a meaningful catalyst to come later this year thanks to the treatment. Executives pointed to a limited market opportunity for IK-930 alone and a long timeline to prove it can provide benefit in a combination regimen. IK-595, meanwhile, is advancing through the clinic a little faster, William Blair noted. "Clear single-agent activity with IK-595 will be needed to generate significant interest and share appreciation beyond the cash balance," the analysts wrote. "Management emphasized that it is enthusiastic about the profile of IK-595 to date and the potential for a more straightforward development path in much large market opportunities."

临床1期蛋白降解靶向嵌合体临床2期

2024-05-28

·GlobeNewswire-Health Care

UPDATE – Ikena Oncology Announces Strategic Update

Ikena to discontinue development of IK-930 IK-595 dose escalation continues in RAS and RAF mutant cancers; Encouraging PK and PD profile shown to date Ended first quarter with $157.3 million; Exploring strategic options to maximize shareholder value BOSTON, May 28, 2024 (GLOBE NEWSWIRE) -- Ikena Oncology, Inc. (Nasdaq: IKNA, “Ikena,” “Company”) today announced discontinuation of the clinical IK-930 program, the Company’s TEAD1- selective Hippo pathway inhibitor and continued clinical development of IK-595, a novel MEK-RAF molecular glue. Concurrently, Ikena is evaluating strategic options for both the Company and its development pipeline. “Ikena is dedicated to thoughtfully putting our capital to work towards impactful treatments for patients, and in doing so building value for our shareholders. Together with our board of directors, we made the difficult decision to wind down the IK-930 program. Going forward, we believe that IK-930’s profile may enable combination opportunities with other targeted agents through partnerships,” commented Mark Manfredi, Ph.D., Chief Executive Officer of Ikena. “Our MEK-RAF molecular glue, IK-595, continues to progress rapidly in the clinic with encouraging early PK and PD data which supports a potentially differentiated therapeutic index. This is key to treating the broad population of patients suffering from RAS and RAF mutant cancers where other MEK inhibitors have failed.” Pipeline & Corporate Updates IK-930: TEAD1-Selective Hippo Pathway Inhibitor Based on a review of clinical data to date, available resources, and the Company’s strategic priorities, the Company decided to discontinue development of IK-930The IK-930 Phase 1 program will begin winddown activities; treatment will continue for patients enrolled to date who have derived benefitThe Company will seek strategic options for the program, including potential partners for development of IK-930 in combination with other targeted agents IK-595: MEK-RAF Molecular Glue The first two cohorts in the Phase 1 study of IK-595 in patients with RAS and RAF mutant cancers have cleared; backfilling in select cohorts is planned for the second half of 2024Promising early pharmacokinetics (PK) and pharmacodynamics (PD) activity has been observed, with dose dependent exposure and target modulation measured in the blood Reached above 80% pERK inhibition at 4 hours post dosing to date, with above 60% inhibition sustained through 24 hours; dose escalation continues Corporate Updates In connection with the discontinuation of IK-930 development, the Company is executing a workforce reduction of approximately 53%$157 million in cash, cash equivalents and marketable securities as of March 31, 2024Concurrently with the continuation of IK-595 development activities, Ikena has begun to explore a range of available strategic alternatives “Ikena is in a strong position to create value through multiple avenues. We have been diligent with our capital expenditure, fortifying a cash position that may unlock new strategic opportunities for the company, in addition to the parallel partnership potential of our pipeline,” said Jotin Marango, M.D., Ph.D., Ikena’s Chief Financial Officer. About Ikena OncologyIkena Oncology® develops differentiated therapies for patients in need that target nodes of cancer growth, spread, and therapeutic resistance. Ikena aims to utilize their depth of institutional knowledge and breadth of tools to efficiently develop the right drug using the right modality for the right patient. To learn more, visit www.ikenaoncology.com. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding: the timing and advancement of our targeted oncology programs, including the timing of updates; our expectations regarding the therapeutic benefit of our targeted oncology programs; our ability to efficiently discover and develop product candidates; our ability to obtain and maintain regulatory approval of our product candidates; expectations with respect to projected cash runway; the anticipated results of our organizational changes; the implementation of our business model; and strategic plans for our business and product candidates. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those risks and uncertainties related to the timing and advancement of our targeted oncology programs; our expectations regarding the therapeutic benefit of our targeted oncology programs; our ability to efficiently discover and develop product candidates; the implementation of our business model, and strategic plans for our business and product candidates, the sufficiency of the Company’s capital resources to fund operating expenses and capital expenditure requirements and the period in which such resources are expected to be available, and other factors discussed in the “Risk Factors” section of Ikena’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, which is on file with the Securities and Exchange Commission (SEC), as updated by any subsequent SEC filings. We caution you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. We disclaim any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent our views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. We explicitly disclaim any obligation to update any forward-looking statements. Ikena Contact:Rebecca Cohenrcohen@ikenaoncology.com

临床1期

100 项与 IK-930 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
晚期恶性实体瘤	临床1期	美国	Ikena Oncology, Inc.	2022-01-07
晚期恶性实体瘤	临床1期	英国	Ikena Oncology, Inc.	2022-01-07
上皮样血管内皮瘤	临床1期	美国	Ikena Oncology, Inc.	2022-01-07
上皮样血管内皮瘤	临床1期	英国	Ikena Oncology, Inc.	2022-01-07
恶性胸膜间皮瘤	临床1期	美国	Ikena Oncology, Inc.	2022-01-07
恶性胸膜间皮瘤	临床1期	英国	Ikena Oncology, Inc.	2022-01-07
间皮瘤	临床1期	美国	Ikena Oncology, Inc.	2022-01-07
间皮瘤	临床1期	英国	Ikena Oncology, Inc.	2022-01-07
实体瘤	临床1期	美国	Ikena Oncology, Inc.	2022-01-07
实体瘤	临床1期	英国	Ikena Oncology, Inc.	2022-01-07

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


GlobeNewswire 人工标引	临床1期	实体瘤	26	IK-930	築築鹽衊網製鏇壓憲鹽(築願壓齋鬱醖齋願壓製) = 簾顧蓋鏇獵膚衊淵醖襯觸鹽糧製簾夢選齋鹽鏇 (範觸鏇淵鏇蓋衊膚積製 )	积极	2023-11-09
				IK-930 (EHE)	鑰範築遞遞範蓋繭壓選(蓋蓋遞顧製鏇範糧淵網) = 鏇齋蓋製積壓範鏇夢築醖齋鏇糧鏇選築餘觸願 (醖糧窪遞獵齋壓獵觸遞 ) 更多