Medicinal Chemistry International

DRUG PATENTS INTERNATIONAL

Lutetium (177Lu) tezuvotide tetraxetan

CAS2613239-73-7

MF C60H92F177LuN12O23Si , 1573.5 g/mol

2-[4-[2-[[(2R)-1-[[(1R)-1-carboxy-5-[[4-[[(4R)-4-carboxy-4-[[(4S)-4-carboxy-4-[[(1S)-1,3-dicarboxypropyl]carbamoylamino]butanoyl]amino]butyl]amino]-4-oxobutanoyl]amino]pentyl]amino]-3-[[4-[ditert-butyl(fluoro)silyl]benzoyl]amino]-1-oxopropan-2-yl]amino]-2-oxoethyl]-7,10-bis(carboxylatomethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetate;lutetium-177(3+)

antineoplastic, 177LU-RHPSMA-10.1, RHPSMA-10.1 LUTETIUM LU-177, FJ9Z7Y8MRW

Lutetium (177Lu) tezuvotide tetraxetan ($^{177}$Lu-rhPSMA-10.1) is an experimental radioligand therapy, developed by Bracco, that targets prostate-specific membrane antigen (PSMA) to treat metastatic castration-resistant prostate cancer. It uses a radiohybrid (rh) PSMA molecule, designed to have high binding affinity to PSMA-positive cancer cells and deliver targeted beta-minus radiation.

Key details:

Mechanism: It binds to PSMA-expressing cells, leading to DNA damage and tumor cell death.
Target: Prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer.
Distinction: It is distinct from the FDA-approved ${177}$Lu-vipivotide tetraxetan (Pluvicto), though it is part of the same class of PSMA-targeted radiopharmaceutical agents.
Status: It has been tested in clinical trials as a potential therapy for advanced prostate cancer, including studies evaluating its efficacy and safety.

It is important to distinguish between the various PSMA-targeted agents, such as vipivotide tetraxetan, which is approved for use.

Lutetium Lu 177 Tezuvotide Tetraxetan is a radioconjugate composed of PSMA-10.1, a prostate-specific membrane antigen (PSMA)-targeting ligand and radiolabeled with the beta-emitting radioisotope lutetium Lu 177 (177Lu), with potential antineoplastic activity against PSMA-expressing tumor cells. Upon intravenous administration, lutetium Lu 177 tezuvotide tetraxetan targets and binds to PSMA-expressing tumor cells. Upon binding, PSMA-expressing tumor cells are destroyed by 177Lu through the specific delivery of beta particle radiation. PSMA, a tumor-associated antigen (TAA) and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on prostate tumor cells as well as a variety of other solid tumors.

An open-label, multicentre, integrated Phase 1 & 2 study to evaluate the safety, tolerability, radiation dosimetry and anti-tumour activity of Lutetium (177Lu) rhPSMA-10.1 injection in men with metastatic castrate-resistant prostate cancer

EudraCT: 2022-002407-37

Phase: Phase 2

Status: Trial now transitioned

Date: 2023-05-22

PAT

https://patents.google.com/patent/WO2024121722A1/en

AS ON OCT2025 4.511 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT

join me on Linkedin

Anthony Melvin Crasto Ph.D – India | LinkedIn

join me on Researchgate

RESEARCHGATE

This image has an empty alt attribute; its file name is research.jpg

join me on Facebook

Anthony Melvin Crasto Dr. | Facebook

join me on twitter

Anthony Melvin Crasto Dr. | twitter

+919321316780 call whatsaapp

EMAIL. amcrasto@gmail.com

//////////////lutetium (177Lu) tezuvotide tetraxetan, antineoplastic, 177LU-RHPSMA-10.1, RHPSMA-10.1 LUTETIUM LU-177, FJ9Z7Y8MRW

#lutetium (177Lu) tezuvotide tetraxetan, #antineoplastic, #177LU-RHPSMA-10.1, #RHPSMA-10.1 LUTETIUM LU-177, #FJ9Z7Y8MRW

DRUG PATENTS INTERNATIONAL

Ranosidenib

CAS 2301974-60-5

MF C15H16F9N5O MW 453.31 g/mol

(1S)-3-[4,6-bis[[(2R)-1,1,1-trifluoropropan-2-yl]amino]-1,3,5-triazin-2-yl]-2,6,6-trifluorocyclohex-2-en-1-ol

(1S)-3-(4,6-bis{[(2R)-1,1,1-trifluoropropan-2-yl]amino}-1,3,5-triazin-2-yl)-2,6,6-trifluorocyclohex-2-en-1-ol
isocitrate dehydrogenase (IDH) inhibitor, antineoplastic, [14C] HMPL-306, HMPL 306, PC64OXS2C2

OriginatorHutchison MediPharma
DeveloperHUTCHMED
ClassAntineoplastics; Small molecules
Mechanism of ActionIsocitrate dehydrogenase 1 inhibitors; Isocitrate dehydrogenase 2 inhibitors
Phase IIIAcute myeloid leukaemia
No development reportedHaematological malignancies; Solid tumours
28 Sep 2025No recent reports of development identified for phase-I development in Haematological-malignancies(Late-stage disease, Second-line therapy or greater) in Spain (PO)
28 Sep 2025No recent reports of development identified for phase-I development in Haematological-malignancies(Late-stage disease, Second-line therapy or greater) in USA (PO)
19 Sep 2025No development reported - Phase-I for Solid tumours (Late-stage disease, Metastatic disease, Second-line therapy or greater) in USA (PO)

Ranosidenib is a small molecule drug. Ranosidenib is under investigation in clinical trial NCT06387069 (A Study to Evaluate HMPL-306 in Patients With IDH1- and IDH2-mutated Acute Myeloid Leukemia). Ranosidenib has a monoisotopic molecular weight of 453.12 Da.

Ranosidenib is an orally bioavailable inhibitor of mutated forms of both isocitrate dehydrogenase type 1 (IDH1, IDH1 [NADP+] soluble) in the cytoplasm and type 2 (IDH2, isocitrate dehydrogenase [NADP+], mitochondrial) in the mitochondria, with potential antineoplastic activity. Upon administration, ranosidenib specifically targets and inhibits mutant forms of IDH1 and IDH2, thereby inhibiting the formation of the oncometabolite 2-hydroxyglutarate (2HG) from alpha-ketoglutarate (a-KG). This prevents 2HG-mediated signaling and leads to both an induction of cellular differentiation and an inhibition of cellular proliferation in tumor cells expressing IDH mutations. IDH1 and 2, metabolic enzymes that catalyze the conversion of isocitrate into a-KG, play key roles in energy production and are mutated in a variety of cancer cell types. Mutant forms of IDH1 and 2 catalyze the formation of 2HG and drive cancer growth by blocking cellular differentiation and inducing cellular proliferation.

A Study of HMPL-306 in Advanced Hematological Malignancies With mIDHCTID: NCT04764474Phase: Phase 1Status: TerminatedDate: 2026-01-29

A Study of HMPL-306 in Advanced Solid Tumors With IDH MutationsCTID: NCT04762602Phase: Phase 1Status: TerminatedDate: 2025-09-16

A Study to Evaluate HMPL-306 in Patients With IDH1or IDH2-mutated Acute Myeloid LeukemiaCTID: NCT06387069Phase: Phase 3Status: RecruitingDate: 2025-08-14

Phase I Study of HMPL-306 for the Treatment of Gliomas With IDH1 and/or IDH2 MutationsCTID: NCT07025018Phase: Phase 1Status: RecruitingDate: 2025-08-01

A Study of HMPL-306 in Patients With IDH1 and/or IDH2 Mutation of Relapsed/Refractory Myeloid Leukemia/NeoplasmsCTID: NCT04272957Phase: Phase 1Status: Unknown statusDate: 2020-06-16

SYN

https://pubs.acs.org/doi/10.1021/acsmedchemlett.4c00625

aReagents and conditions: (i) Na2PdCl4, DTBPPS, K2CO3, MeCN, H2O, 60 ℃; (ii) TBSOTf, Et3N,
DCM, 0~5 ℃; Selectfluor®, MeCN, 0~5 ℃; (iii) TBSOTf, Et3N, DCM, 0~5 ℃; Selectfluor®,
MeCN, 0~5 ℃; (iv) NaBH4, CeCl3·7H2O, EtOH, 0 ℃; (v) SFC separation.

Pat

Cycloolefin substituted heteroaromatic compounds and their use

Publication Number: US-2021363115-A2

Priority Date: 2017-09-07

PAT

https://patentscope.wipo.int/search/en/detail.jsf?docId=US325708969&_cid=P22-MMFPFM-26361-1

Intermediate I-3

6-Chloro-N²,N⁴-bis((R)-1,1,1-trifluoropropan-2-yl)-1,3,5-triazine-2,4-diamine

At 0° C., to a flask were added 1,4-dioxane (50 mL), 2,4,6-trichloro-1,3,5-triazine (1.84 g, 10 mmo), (R)-1,1,1-trifluoropropan-2-amine hydrochloride (2.99 g, 20 mmol) and DIEA (5.17 g, 40 mmol). The reaction was heated to 60° C. and stirred for 4 hours. After the reaction was completed, the mixture was condensed and purified by flash column chromatography (eluting with gradient water/MeOH=100:0-0:100) to give Intermediate I-3 as yellow solid (2.50 g, yield: 74%). MS (m/z): 338.0 [M+H] ⁺

Compounds 197 and 198

3-(4,6-Bis(((R)-1,1,1-trifluoropropan-2-yl)amino)-1,3,5-triazin-2-yl)-2,6,6-trifluorocyclohex-2-en-1-ol, optically pure diastereoisomers

The Compound 196 was resolved by chiral HPLC to provide a pair of optically pure diastereoisomers, Compounds 197 and 198 (Chiral HPLC conditions: Preparation instrument: Shimadzu LC-10AD vp; Column: Daicel AD-H(250 mm*30 mm, 5 um); mobile phase: n-heptane/isopropanol=90/10; flow rate: 40 mL/min; column temperature: 40° C.). The first eluent (RT=4.203 min) was concentrated and purified by flash column chromatography (eluting with gradient PE/EA=100:0-0:100) to give a compound named as Compound 197, de %=99.27%, MS (m/z): 454.1 [M+1] ⁺. The second eluent (RT=5.906 min) was concentrated and purified by flash column chromatography (eluting with gradient PE/EA=100:0-0:100) to give a compound named as Compound 198, de %=97.82%, MS (m/z): 454.2 [M+1] ⁺.

Compound 197: ¹H NMR (400 MHz, CD ₃OD): δ 5.00-4.86 (m, 2H), 4.36-4.17 (m, 1H), 2.80-2.65 (m, 1H), 2.58-2.42 (m, 1H), 2.25-2.05 (m, 2H), 1.37-1.31 (m, 6H).

Compound 198: ¹H NMR (400 MHz, CD ₃OD): δ 5.00-4.86 (m, 2H), 4.36-4.17 (m, 1H), 2.80-2.65 (m, 1H), 2.58-2.42 (m, 1H), 2.25-2.05 (m, 2H), 1.37-1.31 (m, 6H).

AS ON FEB2026 4.574 LAKHS VIEWS ON BLOG WORLDREACH AVAILABLEFOR YOUR ADVERTISEMENT

join me on Linkedin

Anthony Melvin Crasto Ph.D – India | LinkedIn

join me on Researchgate

RESEARCHGATE

join me on Facebook

Anthony Melvin Crasto Dr. | Facebook

join me on twitter

Anthony Melvin Crasto Dr. | twitter

+919321316780 call whatsaapp

EMAIL. amcrasto@gmail.com

/////////ranosidenib, isocitrate dehydrogenase (IDH) inhibitor, antineoplastic, [14C] HMPL-306, HMPL 306, PC64OXS2C2

#ranosidenib, #isocitrate dehydrogenase (IDH) inhibitor, #antineoplastic, #[14C] HMPL-306, #HMPL 306, #PC64OXS2C2

DRUG PATENTS INTERNATIONAL

Andamertinib

CAS 2254145-43-0

MF C31H36N8O3 MW568.7 g/mol

N-[4-methoxy-2-[4-(3-methoxyazetidin-1-yl)piperidin-1-yl]-5-[[6-(1-methylindazol-5-yl)pyrimidin-4-yl]amino]phenyl]prop-2-enamide

N-(4-methoxy-2-[4-(3-methoxyazetidin-1-yl)piperidin-1-yl]-5-{[6-(1-methyl-1H-indazol-5-yl)pyrimidin-4-yl]amino}phenyl)prop-2-enamide
epidermal growth factor receptor tyrosine kinase inhibitor, antineoplastic, PLB 1004, 5X3KAG7ZBW

Andamertinib (also known as PLB1004) is an investigational, orally bioavailable, and irreversible small-molecule inhibitor of the epidermal growth factor receptor (EGFR). It is primarily being developed to treat non-small cell lung cancer (NSCLC) with specific genetic mutations.

Key Clinical & Therapeutic Features

Target Mutations: It specifically targets EGFR exon 20 insertion (ex20ins) mutations, which are often resistant to standard first- and second-generation EGFR inhibitors.
Broad Selectivity: Beyond ex20ins, it also shows activity against classical mutations like Del19, L858R, and the resistance mutation T790M.
Brain Penetration: Andamertinib is designed to cross the blood-brain barrier, making it potentially effective for patients with brain metastases.
Clinical Performance: In phase 2 studies (e.g., the KANNON study), it demonstrated a confirmed objective response rate (ORR) of 42.7% and a median progression-free survival of 6.2 months in pretreated patients.

Regulatory Status (as of Early 2026)

China: A New Drug Application (NDA) was accepted by the National Medical Products Administration (NMPA) in May 2025 and granted priority review for treating NSCLC with EGFR ex20ins mutations.
Global: It remains in various stages of clinical trials globally, including studies for first-line treatment and combination therapies with other agents like vebreltinib.

Andamertinib is an orally bioavailable, mono-anilino-pyrimidine, mutant-selective epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon oral administration, andamertinib targets, binds to and irreversibly inhibits the activity of various EGFR mutations, including exon 20 insertion (Ex20ins) activating mutations, the gatekeeper mutation T790M, ExDel19, and L858R. This prevents EGFR-mediated signaling, induces cell death and inhibits tumor growth in tumor cells expressing these EGFR mutations. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.

SYN

[WO2018228446A1]