Delving into the Latest Updates on SCB-01A with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

+ [6]

Target

Tubulin

Action

inhibitors

Mechanism

Tubulin inhibitors

Therapeutic Areas

Neoplasms

Active Indication

Head and Neck Neoplasms

Inactive Indication

Advanced Malignant Solid NeoplasmSquamous cell carcinoma of head and neck metastatic

Originator Organization

SynCore Biotechnology Co., Ltd.

Active Organization

Sinphar Pharmaceutical Co. Ltd.

Inactive Organization

SynCore Biotechnology Co., Ltd.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC19H19NO5

InChIKeyUZJVBXKFBQNDTQ-UHFFFAOYSA-N

CAS Registry613679-11-1

AbstractLessons LearnedSCB01A is a novel microtubule inhibitor with vascular disrupting activity. This first-in-human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity. SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.BackgroundSCB01A, a novel microtubule inhibitor, has vascular disrupting activity.MethodsIn this phase I dose-escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m2 to the maximum tolerated dose (MTD) based on dose-limiting toxicity (DLT). SCB01A-induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints.ResultsTreatment-related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m2 cohort; grade 3 gastric hemorrhage in the 6.5 mg/m2 cohort; grade 2 thromboembolic event in the 24 mg/m2 cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m2 cohort. The MTD was 24 mg/m2, and average half-life was ~2.5 hours. The area under the curve-dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A-induced neurotoxicity was reversible in vitro.ConclusionThe MTD of SCB01A was 24 mg/m2 every 21 days; it is safe and tolerable in patients with solid tumors.

29 May 2018·Journal of Chemical Information and ModelingQ2 · CHEMISTRY

Reliable and Performant Identification of Low-Energy Conformers in the Gas Phase and Water

Q2 · CHEMISTRY

Article

Author: Cavasin, Anna Theresa ; Göller, Andreas H. ; Hillisch, Alexander ; Schneckener, Sebastian ; Uellendahl, Felix

Prediction of compound properties from structure via quantitative structure-activity relationship and machine-learning approaches is an important computational chemistry task in small-molecule drug research. Though many such properties are dependent on three-dimensional structures or even conformer ensembles, the majority of models are based on descriptors derived from two-dimensional structures. Here we present results from a thorough benchmark study of force field, semiempirical, and density functional methods for the calculation of conformer energies in the gas phase and water solvation as a foundation for the correct identification of relevant low-energy conformers. We find that the tight-binding ansatz GFN-xTB shows the lowest error metrics and highest correlation to the benchmark PBE0-D3(BJ)/def2-TZVP in the gas phase for the computationally fast methods and that in solvent OPLS3 becomes comparable in performance. MMFF94, AM1, and DFTB+ perform worse, whereas the performance-optimized but far more expensive functional PBEh-3c yields energies almost perfectly correlated to the benchmark and should be used whenever affordable. On the basis of our findings, we have implemented a reliable and fast protocol for the identification of low-energy conformers of drug-like molecules in water that can be used for the quantification of strain energy and entropy contributions to target binding as well as for the derivation of conformer-ensemble-dependent molecular descriptors.

13 Nov 2017·Angewandte Chemie International EditionQ1 · CHEMISTRY

Fully Automated Quantum‐Chemistry‐Based Computation of Spin–Spin‐Coupled Nuclear Magnetic Resonance Spectra

Q1 · CHEMISTRY

Article

Author: Pisarek, Jana ; Seibert, Jakob ; Grimme, Stefan ; Hansen, Andreas ; Bannwarth, Christoph ; Dohm, Sebastian ; Pracht, Philipp ; Neese, Frank

AbstractWe present a composite procedure for the quantum‐chemical computation of spin–spin‐coupled 1H NMR spectra for general, flexible molecules in solution that is based on four main steps, namely conformer/rotamer ensemble (CRE) generation by the fast tight‐binding method GFN‐xTB and a newly developed search algorithm, computation of the relative free energies and NMR parameters, and solving the spin Hamiltonian. In this way the NMR‐specific nuclear permutation problem is solved, and the correct spin symmetries are obtained. Energies, shielding constants, and spin–spin couplings are computed at state‐of‐the‐art DFT levels with continuum solvation. A few (in)organic and transition‐metal complexes are presented, and very good, unprecedented agreement between the theoretical and experimental spectra was achieved. The approach is routinely applicable to systems with up to 100–150 atoms and may open new avenues for the detailed (conformational) structure elucidation of, for example, natural products or drug molecules.

100 Deals associated with SCB-01A

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Squamous cell carcinoma of head and neck metastatic	Preclinical	Taiwan Province	SynCore Biotechnology Co., Ltd.	01 Sep 2015
Head and Neck Neoplasms	Discovery	Taiwan Province	SynCore Biotechnology Co., Ltd.	24 Sep 2015
Advanced Malignant Solid Neoplasm	Discovery	Taiwan Province	SynCore Biotechnology Co., Ltd.	01 Apr 2011

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02488629 (CTgov)	Phase 2	Squamous cell carcinoma of head and neck metastatic	5	SCB01A (Run-in Phase I (Dose Escalation Phase): 3.25 mg/m² (Dose 1))	gbenxmwpaz(nbnimpglco) = zzcmfvbniz qrujahlcwq (iutwkiekok, nnbvgichru - xiopwvdkyt) View more	-	27 Jun 2023
NCT02488629 (CTgov)	Phase 2	Squamous cell carcinoma of head and neck metastatic	5	SCB01A (Run-in Phase I (Dose Escalation Phase): 12 mg/m² (Dose 2))	ujucudiurp(zhmbefetyw) = ccqaqlwsdk npheppzpix (webpxwobwt, yetblckkjd - bswceurpmx) View more	-	27 Jun 2023
NCT03020823 (CTgov)	Phase 2	Squamous cell carcinoma of head and neck metastatic	10	SCB01A	jhypydqpqe(iwqqvigtxc) = pxulcxqybk nkkhtrvdqv (ccafcshkqm, yeohjhxfsm - irzrjqowwu) View more	-	02 Jun 2023
NCT01159522 (ASCO2017)	Phase 1	Refractory Malignant Solid Neoplasm	33	SCB01A	(kaakcshwkc) = All adverse events were classified according to the CTCAE V4.0. nuzkuxnytv (mdiledahme )	-	30 May 2017
AACR2013	Not Applicable	Ovarian Cancer	-	BPR0L075	ydjlynlxps(znvibmacpd) = mreovorklv egadcdntqd (nqqnsztbxz )	-	15 Apr 2013