Lorlatinib (PF-06463922) NEW
| Price | $8 | $3 | $1 |
| Package | 1KG | 25KG | 100KG |
| Min. Order: | 1KG |
| Supply Ability: | g-kg-tons, free sample is available |
| Update Time: | 2024-03-29 |
Product Details
| Product Name: Lorlatinib (PF-06463922) | CAS No.: 1454846-35-5 |
| Min. Order: 1KG | Purity: 99% |
| Supply Ability: g-kg-tons, free sample is available | Release date: 2024/03/29 |
| Lead time: In stock, ready for shipment | IIn stock, r: bag/bottle/drum/IBC |
| bag/bottle: By express, by air, by sea | Origin: Manufacturer, advantage product |
| COA, MS: Available, contact us for details | NAME: Sun |
1. Materials information
| Name | pf-06463922 |
|---|---|
| Synonym | More Synonyms |
| Description | Lorlatinib is a potent, dual ALK/ROS1 inhibitor, with Kis of 0.02 nM, 0.07 nM, and 0.7 nM for ROS1, wild type ALK, and ALK-L1196M, respectively. |
|---|---|
| Related Catalog | Signaling Pathways >> Protein Tyrosine Kinase/RTK >> ALK Research Areas >> Cancer |
| Target | Ki: < 0.02 nM (ROS1), < 0.07 nM (ALK WT), 0.7 nM (ALK L1196M) |
| In Vitro | Lorlatinib demonstrates significant cell activity against ALK and a large set of ALK clinical mutations with IC50 ranging from 0.2 nM-77 nM[1]. Lorlatinib significantly inhibits cell proliferation and induces cell apoptosis in the HCC78 human NSCLC cells harboring SLC34A2-ROS1 fusions and the BaF3-CD74-ROS1 cells expressing human CD74-ROS1[2]. Lorlatinib also shows potent growth inhibitory activity and induces apoptosis in the NSCLC cells harboring either non-mutant ALK or mutant ALK fusions[3]. |
| In Vivo | In rats, Lorlatinib displays low plasma clearance, a moderate volume of distribution, a reasonable half-life, low propensity for p-glycoprotein 1-mediated efflux and a bioavailability of 100%[1]. In vivo, Lorlatinib shows cytoreductive antitumor efficacy in the NIH3T3 xenograft models expressing human CD74-ROS1 and Fig-ROS1 via inhibition in ROS1 phosphorylation and the downstream signaling molecules, as well as inhibition of the cell cycle protein Cyclin D1 in tumors[2]. In vivo, Lorlatinib also demonstrates marked antitumor activity in mice bearing tumor xenografts expressing EML4-ALK, EML4-ALK-L1196M, EML4-ALK-G1269A, EML4-ALK-G1202R or NPM-ALK[3]. |
| Kinase Assay | Recombinant human wild-type and mutant ALK kinase domain proteins (amino acids 1093–1411) are produced in-house using baculoviral expression, preactivated via autophosphorylation with MgATP, and assayed for kinase activity using a microfluidic mobility shift assay. The reactions contained 1.3 nM wild-type ALK or 0.5 nM mutant ALK (appropriate to produce 15-20% phosphorylation of peptide substrate after 1 h of reaction), 3 μM 5-FAM-KKSRGDYMTMQIG-CONH2), 5 mM MgCl2, and the Km level of ATP in 25 mM Hepes, pH 7.1. The inhibitors are shown to be ATP-competitive from kinetic and crystallographic studies. The Ki values are calculated by fitting the conversion (%) to a competitive inhibition equation. ROS1 enzyme is assayed as described above for ALK, except using 0.25 nM recombinant human ROS1 catalytic domain (amino acids 1883-2347). Kinase inhibitor selectivity is evaluated using a 206-kinase panel. |
| Cell Assay | Cells are seeded in 96-well plates in growth medium containing 10% FBS and are cultured overnight at 37°C. The following day, serial dilutions of Lorlatinib or appropriate controls are added to the designated wells, and cells are incubated at 37°C for 72 h. A CellTiter-Glo assay is performed to determine the relative cell numbers. IC50 values are calculated by concentration-response curve fitting using a four-parameter analytical method. |
| Animal Admin | De novoGBM tumorigenesis is initiated in LSL-FIG-ROS1;Cdkn2a−/−;LSL-Luc mice through intracranial stereotactic injections of Adeno-Cre as described previously. Tumor development is monitored using BLI as described below. Once tumors reach a given size (107 p-1·s-1·cm-2·sr-1), animals are randomLy enrolled into vehicle control or 3-, 7-, or 14-d treatment with the indicated doses of Lorlatinib. Drug is administered through s.c. implanted Alzet osmotic pumps. After treatment, mice are killed, GBM tumors are microdissected, and tissues are flash-frozen in liquid N2. The remaining brains are processed for histology. |
| References | [1]. Johnson TW, et al. Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinas [2]. Zou HY, et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3493-8 [3]. Zou HY, et al. PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):3493-8. |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Boiling Point | 675.0±55.0 °C at 760 mmHg |
| Molecular Formula | C21H19FN6O2 |
| Molecular Weight | 406.413 |
| Flash Point | 362.1±31.5 °C |
| Exact Mass | 406.155365 |
| PSA | 110.06000 |
| LogP | 1.24 |
| Vapour Pressure | 0.0±2.1 mmHg at 25°C |
| Index of Refraction | 1.687 |
| Storage condition | -20℃ |
| RIDADR | NONH for all modes of transport |
|---|
| UNII:OSP71S83EU |
| (R)-2<sup>6</sup>-amino-5<sup>5</sup>-fluoro-1<sup>1</sup>,4,7-trimethyl-6-oxo-1<sup>1</sup>H-3-oxa-7-aza-2(3,5)-pyridina-1(4,3)-pyrazola-5(1,2)-benzenacyclooctaphane-1<sup>5</sup>-carbonitrile |
| 2H-8,4-Methenopyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile, 7-amino-12-fluoro-10,15,16,17-tetrahydro-2,10,16-trimethyl-15-oxo-, (10R)- |
| (16R)-19-Amino-13-fluoro-4,8,16-trimethyl-9-oxo-17-oxa-4,5,8,20-tetraazatetracyclo[16.3.1.0.0]docosa-1(22),2,5,10,12,14,18,20-octaene-3-carbonitrile |
| lorlatinib |
| (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-4,8- methenopyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile |
| PF06463922 |
| PF-06463922 |
2. Packaging of materials
For powders: normal is 25kgs/Drum or bag, or larger/smaller package as request.
For liquids: normal 25kgs/drum, 180-300kgs/bucket, or IBC, determined by the nature of the product.
Or smaller package 1kg/bottle, 10kgs/bottle as request.
3. Shipping & Delivery
By Express
Provide door to door service
Suitable for goods under 50kg
Delivery: 3-7 days
Cost: low cost
By Air
Provide airport to airport service
Suitable for goods over 50kg
Delivery: 3-14 days
Cost: high cost
By Sea
Provide seaport to seaport service
Suitable for goods over 100kg
Delivery: 2-45 days
Cost: low cost
4. Contact information
For more details, pls contact us freely.
Email address: Sun@fdachem.com
Mob: 86 13526505137
WhatsApp/Skype/Wechat/LINE: 86 13526505137
Company Profile Introduction
Henan Fengda Chemical Co., Ltd. is located in the High-tech Development Zone of Henan Province. Specializing in the production and sales of various fine chemical products required for industrial production, including chemical raw materials, organic raw materials, petrochemicals, chemical reagents, solvents, catalysts, and additives, etc.
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China
- Since: 2023-02-10
- Address: Room 01, 2288 E05, Building 14, East Henan University, Science and Technology Park, 279 Xisanhuan Ro
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