monzosertib (AS-0141) / SBI Biotech, Carna Biosci - LARVOL DELTA

Triplet combination of monzosertib, a potent CDC7 inhibitor, with DNMT and BCL2 inhibitors is highly active in human AML xenograft mouse models (AACR 2025) - "Thus, CDC7 has been recognized as a potential drug target for treating cancers.Monzosertib (AS-0141) is a potent, selective, orally bioavailable small molecule inhibitor of CDC7, currently under Phase I clinical study in patients with advanced, metastatic, relapsed or refractory malignancies. Monzosertib demonstrated significant synergistic activity in combination with DNMTi (azacitidine or decitabine) and venetoclax in both in vitro and in vivo human AML models. The triplet combination of monzosertib with DNMTi (azacitidine or decitabine) and venetoclax was well-tolerated in these mouse AML models, suggesting the triplet therapy of monzosertib combined with the standard of care (DNMTi plus venetoclax) for AML patients may provide a new therapeutic opportunity in AML."

IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CDC7

Synergistic effect of the CDC7 inhibitor, monzosertib (AS-0141) with current therapies in AML models (AACR 2024) - "DNA metyltransferase (DNMT) inhibitors (azacitidine or decitabine) and BCL2 inhibitor (venetoclax) were evaluated for their synergistic/antagonistic effects in combination with monzosertib against human AML cell lines (THP-1, HL-60, MV4-11, MOLM-14, TF-1, U-937 and NOMO-1). Monzosertib, a selective CDC7 inhibitor, demonstrated strong antiproliferative activity against human AML cell lines, both as a single agent and in combination with standard therapies. Monzosertib exerts synergistic antitumor effect with venetoclax in a human AML xenograft mouse model. These results suggest that monzosertib has a potential to enhance the antitumor efficacy of standard of care agents for AML patients."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • CDC7

Discovery of AS-0141, a Potent and Selective Inhibitor of CDC7 Kinase for the Treatment of Solid Cancers. (PubMed, J Med Chem) - "Oral administration of 24 demonstrated robust in vivo antitumor efficacy in a colorectal cancer xenograft model. Compound 24 (AS-0141) is currently in phase I clinical trials for the treatment of solid cancers."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

The Efficacy of Plant-Based Ionizers in Removing Aerosol for COVID-19 Mitigation. (PubMed, Research (Wash D C)) - "The aerosol removal rate was quantified in terms of ACH (air changes per hour) and CADR- (clean air delivery rate-) equivalent unit, with ACH as high as 12 and CADR as high as 141 ft/minute being achieved by a plant-based ionizer in a small isolated room. This work provides an important and timely guidance on the effective deployment of ionizers in minimizing the risk of COVID-19 spread via airborne aerosol, especially in a poorly-ventilated environment."

Clinical • Journal • Infectious Disease • Novel Coronavirus Disease

Rational design of metal-binding sites in domain-swapped myoglobin dimers. (PubMed, J Inorg Biochem) - "On the other hand, Co-bound and Zn-bound K79H/G80A/H81A Mb exhibited tetrahedral metal-coordination structures, where His79, His82, Asp141, and a HO/OH molecule coordinated to the metal ion. The Co-bound site exists deep inside the protein in the K79H/G80A/H81A Mb dimer, which may allow the unique tetrahedral coordination for the Co ion. These results show that we can utilize domain swapping to construct artificial metalloproteins."

Journal • Myoglobin

Nutraceutical phycocyanobilin binding to catalase protects the pigment from oxidation without affecting catalytic activity. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "The docking study results indicated that the ligand most likely binds to amino acid residues (Asn141, Arg 362, Tyr369 and Asn384) near the cavity between the enzyme homotetramer subunits not related to the active site. Finally, complex formation protects the pigment from free-radical induced oxidation (bleaching), suggesting possible prolongation of its half-life and bioactivity in vivo if bound to catalase."

Journal • CAT

A medicolegal approach to the very rare Auto-Brewery (endogenous alcohol fermentation) syndrome. (PubMed, Traffic Inj Prev) - "His blood alcohol level was measured as 160 mg/dl at the time of admission for monitoring and as 141 mg/dl, 322 mg/dl, 208 mg/dl and 279 mg/dl after two hours, six hours, 12 hours and 20 hours, respectively...On the other hand, genuine patients suffering from this condition may be caught by traffic control and become victims of the condition. For that reason, a meticulous and planned approach should be taken to verify the condition and to ensure that it is not overlooked."

Journal • Gastrointestinal Disorder

Transition-state vibrational analysis and isotope effects for COMT-catalyzed methyl transfer. (PubMed, J Am Chem Soc) - "Average valence force constants for the COMT TS show significant differences from early BEBOVIB estimates which were used in support of the compression hypothesis for catalysis. There is no correlation between TS IPFRs and the non-bonded distances for close contacts between the S atom of SAM and Tyr68 or between any of the H atoms of the transferring methyl group and either Met40 or Asp141."

Journal

Genetic variants in IL4RA, IL6 and IL12B genes and susceptibility to hepatitis B and C virus infections among Iraqi patients. (PubMed, J Med Virol) - "A total of 220 viral hepatitis patients were enrolled in the study (113 HBV and 107 HCV), as well as 141 healthy subjects...In conclusion, the study supports the concept that IL6 variant is associated with susceptibility to HBV and HCV infections among Iraqis. Risk of HBV infection is further associated with IL6 variant."

Clinical • Journal • Hepatitis B • Hepatitis C Virus • Infectious Disease • IL4R • IL6 • PCR

Polymeric Nanoparticles for Selective Protein Recognition by using Thiol-ene Mini-emulsion Photopolymerization. (PubMed, J Biomater Sci Polym Ed) - "Morphological investigations exhibited that the particle size of the MIP-NPs, increased compared to the corresponding NIPs and the mean particle diameter by number was measured as 141 nm with narrow distribution...In addition, the rebinding ability of MIP-NPs was much bigger than that of the corresponding NIPs. ELISA results showed that MIPs interact particularly with the myoglobin and show little affinity for BSA in competitive binding experiments."

Journal • Myoglobin

Process development for the degradation of textile azo dyes (mono-, di-, poly-) by advanced oxidation process - Ozonation: Experimental & partial derivative modelling approach. (PubMed, J Environ Manage) - "The rate of degradation for all the three dyes at the optimal condition followed pseudo-first order kinetics with the rate of reaction as 141 mg/L.min, 197.2 mg/L.min and 216.6 mg/Lmin. The predicted model was also evaluated by partial derivative-based equation modelling and experimental approach. The reliability and applicability of the developed process were confirmed by degrading the synthetic mixed dye effluent."

Journal

Evaluation of fundus autofluorescence ımaging of diabetic patients without retinopathy. (PubMed, Arq Bras Oftalmol) - "Fundus autofluorescence imaging analysis revealed that diabetic patients without retinopathy have significant fluorescence alterations. Therefore, a noninvasive imaging technique, such as fundus autofluorescence, may be valuable for evaluation of the retina of diabetic patients without retinopathy."

Clinical • Journal

Identification of Antidiabetic Metabolites from Paederia foetida L. Twigs by Gas Chromatography-Mass Spectrometry-Based Metabolomics and Molecular Docking Study. (PubMed, Biomed Res Int) - "α-Amylase-n-hexadecanoic acid exhibited the lowest binding energy of -2.28 kcal/mol with two hydrogen bonds residue, namely, LYS178 and TYR174, along with hydrophobic interactions involving PRO140, TRP134, SER132, ASP135, and LYS172. The complex consists of one hydrogen bond interacting residue, ARG437, and hydrophobic interactions with ALA444, ASP141, GLN438, GLU432, GLY374, LEU373, LEU433, LYS352, PRO347, THR445, HIS348, and PRO351. The study provides informative data on the potential antidiabetic inhibitors identified in Paederia foetida twigs, indicating the plant has the therapeutic effect properties to manage diabetes."

Journal

Evidence Underpinning the U.S. Government-Mandated Hemodynamic Interventions for Sepsis: A Systematic Review. (PubMed, Ann Intern Med) - "...The Severe Sepsis and Septic Shock Early Management Bundle (SEP-1), the sepsis performance measure introduced in 2015 by the Centers for Medicare & Medicaid Services (CMS), requires the reporting of up to 5 hemodynamic interventions, as many as 141 tasks, and 3 hours to document for a single patient...National Institutes of Health. (PROSPERO: CRD42016052716)."

CMS • Journal • Medicaid • Medicare • Reimbursement • Review

Sierra Oncology launches campaign exploring non-dilutive strategic options to support development of its DDR assets (BioSpace) - "Sierra plans to launch the MOMENTUM Phase 3 clinical trial in Q4 2019 to support potential registration of the momelotinib on a global basis. The randomized double-blind trial is designed to enroll 180 myelofibrosis patients who are symptomatic, anemic and have been treated previously with a JAK inhibitor. Dr. Srdan Verstovsek, MD, PhD...has been named Chief Investigator of the MOMENTUM trial."

Integration of fluorescence imaging and electrochemical biosensing for both qualitative location and quantitative detection of cancer cells. (PubMed, Biosens Bioelectron) - "...ITO electrode is firstly modified by AS1141 aptamer, which could selectively bind to nucleolin overexpressed on the surface of a model breast cancer cell, MCF-7 cell line...Therefore, our method allows noninvasive fluorescence imaging and amplified electrochemical detection using a single labeling platform, providing a biocompatible and highly specific method for adequate analysis of cancer cells. Experimental results demonstrate that strong red fluorescence of DNA-AgNCs clearly displays the loading of cancer cells on ITO electrode after dual recognition, and amplified electrochemical signals of DNA-AgNCs enable improved sensitivity toward quantitative analysis with a detection limit of 3 cells."

Journal

CDC7 kinase inhibition by SRA141 induces a potentially novel caspase-dependent tumor cell apoptosis associated with altered DNA replication and cell cycle dynamics (AACR 2019) - "Moreover, inhibition of Aurora B kinase, which regulates mitotic progression, strongly synergized with SRA141 in caspase-dependent cancer cell killing. Taken together, our findings indicate that the mechanism of cytotoxicity of CDC7 inhibitors is distinct from agents that cause replication fork collapse or inhibit CDKs, and thus may define a new class of cancer therapeutic agents that synergize with drugs that target certain mitotic pathways."

Late-breaking abstract

Sierra reports late-breaking SRA141 preclinical data in poster at AACR 2019 (PRNewswire) - “Sierra Oncology, Inc…reported preclinical data for its novel oral Cdc7 inhibitor, SRA141, in a late-breaking poster being presented today at the American Association of Cancer Research (AACR) Annual Meeting 2019 in Atlanta, Georgia…Prior studies demonstrated that SRA141 potently and selectively inhibits Cdc7, resulting in robust anti-tumor efficacy in colorectal xenograft models, however, the compound's exact mechanism of action has not been characterized previously."

Preclinical

Sierra Oncology announces late-breaking oral and poster presentations at AACR 2019 for SRA737 and SRA141 preclinical data (PRNewswire) - "Sierra Oncology...announced that an abstract reporting preclinical data for SRA737 + LDG, its Chk1 inhibitor plus low dose gemcitabine (LDG), in combination with immunotherapy, has been selected for a late-breaking oral presentation at the American Association of Cancer Research (AACR) Annual Meeting 2019, to be held in Atlanta, Georgia from March 29 to April 3. In addition, a late-breaking abstract reporting preclinical data for Sierra's Cdc7 inhibitor, SRA141, has been selected for a poster presentation at AACR 2019."

Preclinical