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On October 24, 2022, Zentalis Pharmaceuticals ("Zentalis") announced plans to launch ZN-c3 and encorafenib
and cetuximab (BEACON regimen) in 1/2 of patients with BRAF V600E-mutated metastatic colorectal cancer (mCRC).
Phase-dose escalation studies
.
This is the first research project between Zentalis and Pfizer, which was announced when Pfizer made a $25 million equity investment in Zentalis
.
If the combination therapy is successful and approved, the combination of ZN-c3 with a drug that targets DNA damage response (DDR) may be another potential treatment option to help improve the lives
of people with BRAF-mutated metastatic colorectal cancer.
ZN-c3ZN-c3 is a potential "first-in-class" oral Wee1 inhibitor designed to induce synthetic lethality in cancer cells and is currently being developed for use in advanced solid tumors
.
Previously, the FDA granted oral ZN-c3 fast-track designation for the treatment of recurrent or persistent uterine serous carcinoma
.
In April 2022, Zentalis presented at the AACR conference data from a Phase 1b clinical trial of ZN-c3 in combination with chemotherapy for patients with platinum-resistant chemotherapy or refractory ovarian cancer, and the results showed that the combination therapy achieved an objective response rate (ORR) of 30.
2% and a disease control rate (DCR)
of 86.
0% in 43 patients whose efficacy could be evaluated.
Wee1 kinase is a key regulator of G2/M checkpoints, achieving G2/M block by phosphorylating CDK1 Tyr15, leaving time
for DNA repair.
Inhibition of Wee1 eliminates cell cycle blockade,
Promote cells to enter the M stage in advance, resulting in replication stress and mitotic disaster, triggering tumor cell apoptosis
.
Wee1 is highly expressed in many cancers, and according to incomplete statistics, there are currently more than ten drugs under research for Wee1, including inhibitors and PROTACs
.
About BRAF V600E
Mutated mCRCBRAF is one of the important proto-oncogenes, and studies have shown that up to 21% of mCRC patients have BRAF mutations, and V600E mutations account for more than
95% of BRAF mutations.
BRAF
Mutant mCRC constitutes a more aggressive malignancy and has a lower
survival rate than non-BRAF mutant mCRC.
Although the BEACON scheme is BRAF
Patients with V600E-mutant mCRC offer a new standard of care, but additional treatment options are limited, so BRAF-mutated mCRC remains a highly unmet therapeutic area
.
Zentalis is a clinical-stage biopharmaceutical company focused on discovering and developing small molecule therapies
that target the basic biological pathways of cancer.
The company actively promotes the diversified pipeline of oncology treatment,
In May 2020, Zhengtengkang Biologics (hereinafter referred to as "Zentera")
was established in China.
In addition to ZN-c3, Zentera is developing and commercializing oncology drug candidates ZN-d5 and ZN-c5
in China.
ZN-d5 is an oral selective inhibitor of B-cell lymphoma 2 (BCL-2) that was originally developed for the treatment of hematologic malignancies and related diseases
.
BCL-2 and BCL-xL
is a protein that plays a key role in the regulation of cell death, and BCL-2 and/or BCL-xL are frequently detected in many cancer types
overexpression, thereby preventing apoptosis
of cancer cells.
BCL-2 inhibitors restore the apoptosis process to normal and become an important target for
cancer treatment.
Currently, the company is working on ZN-d5 in AML and non-Hodgkin lymphoma
Phase 1 trials in patients with NHL, as well as 1/2 trials in patients with relapsed or refractory light chain (AL) amyloidosis, will also include combination therapies
in future clinical development.
ZN-c5 is a potential best-in-class orally selective estrogen receptor degrader
(SERD), which is being developed for the treatment of ER+/HER2- advanced or metastatic breast cancer
.
ER+/HER2 - Breast cancer dependent on estrogen receptor (ER)
To promote tumor growth and survival, currently approved hormone therapy SERD has limitations, creating opportunities
to develop differentiated drug candidates.
The company designed the ZN-c5
to overcome these limitations, including in drug
design and oral convenience.
Zentalis Pharmaceuticals Announces First ZN-c3 Clinical Development Collaboration with Pfizer
