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Abstrak :
Checkpoint kinase 1 (Chk1) merupakan protein yang berperan dalam proses respon kerusakan DNA, yaitu mengkoordinasi respon kerusakan DNA. Chk1 terekspresi pada kanker kolorektal dan Chk1 berkontribusi dalam resistensi terapi kanker kolorektal. Chk1 mencegah masuknya sel DNA yang rusak atau tidak tereplikasi sempurna dalam tahap mitosis ketika sel ditantang oleh agen perusak DNA, seperti terapi radiasi dan agen kemoterapi. Maka dari itu, inhibisi Chk1 dapat menjadi metode untuk pengobatan kanker. HerbalDB merupakan pangkalan data yang senyawa bahan alam Indonesia yang dibuat oleh Fakultas Farmasi Universitas Indonesia. Penelitian senyawa HerbalDB yang berpotensi sebagai inhibitor Chk1 belum pernah dilakukan. Maka, dilakukan penelitian secara in silico dengan metode penapisan virtual dari pangkalan dari HerbalDB untuk mendapatkan kandidat inhibitor Chk1. Makromolekul Chk1 dengan ID 2R0U yang digunakan diperoleh dari situs RCSB PDB. Parameter yang diperoleh dari hasil optimasi dan validasi untuk melakukan penapisan virtual adalah menggunakan AutoDock dalam PyRx dengan ukuran grid box 60 x 60 x 60 dan evaluasi energi maksimum short (250.000). Dari hasil penapisan virtual, diperoleh 16 senyawa HerbalDB yang memiliki nilai ∆G terendah, yaitu (-)-Kurin, Folitenol, Mangostenon A, Rubranin, 6-Deoksoteasteron, (+)-Thalrugosin, Yamogenin, Isokondodendrin, Limasin, Isoarborinol, Sapogenin, alfa-Amirin, Neriifolin, Siklomorusin, Cassiamin C, beta-Kriptosantin dengan rentang nilai ∆G -11,34 hingga -10,01 kkal/mol. Sebagian besar senyawa tersebut berinteraksi dengan residu asam amino pada situs aktif makromolekul Chk1, yaitu Cys87, Asp148, Glu55, dan Lys38. Hasil tersebut menunjukkan bahwa 16 senyawa tersebut memiliki potensi untuk menjadi kandidat inhibitor Chk1. ......Checkpoint kinase 1 (Chk1) is a target that plays a role in the DNA damage response process, namely coordinating the DNA damage response. Chk1 is expressed in colorectal cancer and Chk1 contributes to colorectal cancer therapy resistance. Chk1 prevents entry of damaged or incompletely replicated DNA cells in the mitotic stage when cells are challenged by DNA-damaging agents, such as radiation therapy and chemotherapeutic agents. Therefore, Chk1 inhibition could be a method for cancer treatment. HerbalDB is a database of Indonesian natural compounds. Research on HerbalDB compounds that have the potential to act as Chk1 inhibitors has never been done. Therefore, an in-silico study was conducted using a virtual screening method from the HerbalDB database to obtain candidates for Chk1 inhibitors. The Chk1 macromolecule with ID 2R0U was obtained from the RCSB PDB site. The parameters obtained from the optimization and validation results to perform virtual screening is using AutoDock in PyRx with a grid box size of 60 x 60 x 60 and a maximum energy evaluation of short (250.000). From the virtual screening, 16 HerbalDB compounds were obtained with the lowest ∆G values: (-)-Curine, Folitenol, Mangostenone A, Rubranine, 6-Deoxoteasterone, (+)-Thalrugosine, Yamogenin, Isochondodendrine, Limacine, Isoarborinol, Sapogenin, alpha-Amyrin, Neriifolin, Cyclomorusin, Cassiamin C, beta-Cryptoxanthin with ∆G values ​​ranging from -11.34 to -10.01 kcal/mol. Most of these compounds interact with the amino acid residues on the active site of Chk1, namely Cys87, Asp148, Glu55, and Lys38. These results indicate that these 16 compounds have the potential to be candidates for Chk1 inhibitors.

Abstrak :
Kanker payudara merupakan salah satu penyebab utama kematian pada wanita di seluruh dunia. Protein HER2 tirosin kinase merupakan salah satu penyebab kanker payudara, yaitu sebesar 30% dari keseluruhan jumlah kasus kanker payudara. Protein HER2 tirosin kinase berperan penting dalam reaksi dimerisasi yang menyebabkan terjadinya autofosforilasi residu tirosin pada domain sitoplasma. Mekanisme ini dapat memicu pertumbuhan sel kanker. Penghambatan aktivitas protein HER2 dapat menjadi alternatif pengobatan kanker payudara. Dalam penelitian ini digunakan senyawa bahan alam flavonoid sebagai basis data dalam perancangan obat kanker payudara secara in silico. Pada perancangan obat secara in silico, dilakukan beberapa tahapan antara lain, preparasi protein, preparasi flavonoid, preparasi standar, simulasi penambatan molekul, pertumbuhan fragmen, serta studi farmakologi kandidat obat. Proses preparasi dan simulasi penambatan molekul dilakukan dengan menggunakan perangkat lunak MOE 2014.09. Tahapan pertumbuhan fragmen dilakukan dengan perangkat lunak Osiris DataWarrior. Studi farmakologi kandidat obat dilakukan dengan perangkat lunak pkCSM, SwissADME, dan AdmetSar. Penelitian ini diharapkan dapat menemukan kandidat ligan penghambat aktivitas protein HER2.

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Breast cancer is one of the main women death cause around the world. HER2 tyrosine kinase protein is one of the causes of breast cancer, which is 30% of the total number of breast cancer cases. The HER2 tyrosine kinase protein plays an important role in the dimerization reaction which causes the autophosphorylation of tyrosine residues in the cytoplasmic domain. This mechanism can trigger the growth of cancer cells. The inhibition of HER2 protein activity can be an alternative treatment for breast cancer. In this study, natural flavonoid compounds were used as a database in designing breast cancer drugs. In drug design using in silico method, several steps were carried out, such as protein preparation, flavonoid preparation, standard preparation, molecular docking simulation, fragment growing process, and pharmacological studies of drug candidates. The preparation and molecular docking simulation process were conducted using MOE 2014.09 software. Fragment growing process were conducted with Osiris DataWarrior software. Pharmacological studies of candidate drugs were carried out with pkCSM, SwissADME, and AdmetSar software. This study is expected to find inhibitor candidates to inhibit the HER2 protein activity.

Abstrak :
This timely guide to kinase inhibitor drug development is the first to cover the entire drug pipeline, from target identification to compound development and clinical application. Edited by the pioneers in the field, on the drug development side this ready reference discusses classical medicinal chemistry approaches as well as current chemical genomics strategies. On the clinical side, both current and future therapeutic application areas for kinase inhibitor drugs are addressed, with a strong focus on oncology drugs. Backed by recent clinical experience with first-generation drugs in the battle against various forms of cancer, this is crucial reading for medicinal, pharmaceutical and biochemists, molecular biologists, and oncologists, as well as those working in the pharmaceutical industry.

Abstrak :
This book provides an overview of different protein kinases, structure, function, regulation, and their role in cancer. It combines kinase biology with chemistry and pharmacology applications for discovery and development of cancer drugs. The text also describes existing and emerging kinase inhibitors, focusing mostly on small molecules but also alternative approaches like therapeutic antibodies. Provides an important resource that helps pharmaceutical researchers understand and work in this dynamic area of cancer drug research.