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Sorafenib

" in MedChemExpress (MCE) Product Catalog:

47

Inhibitors & Agonists

1

Natural
Products

5

Isotope-Labeled Compounds

Cat. No. Product Name Target Research Areas Chemical Structure
  • HY-10201
    Sorafenib
    Maximum Cited Publications
    260 Publications Verification

    Bay 43-9006

    		 Raf VEGFR FLT3 Autophagy Apoptosis Ferroptosis Cancer
    Sorafenib (Bay 43-9006) is a potent and orally active Raf inhibitor with IC50s of 6 nM and 20 nM for Raf-1 and B-Raf, respectively. Sorafenib is a multikinase inhibitor with IC50s of 90 nM, 15 nM, 20 nM, 57 nM and 58 nM for VEGFR2, VEGFR3, PDGFRβ, FLT3 and c-Kit, respectively. Sorafenib induces autophagy and apoptosis. Sorafenib has anti-tumor activity. Sorafenib is a ferroptosis activator .
    Sorafenib
  • HY-W048413
    Sorafenib impurity 2

    		Drug Intermediate Others
    Sorafenib impurity 2 is an impurity of Sorafenib (HY-10201).
    Sorafenib impurity 2
  • HY-10201B
    Sorafenib impurity 3

    		Drug Intermediate Others
    Sorafenib impurity 3 is an impurity of Sorafenib (HY-10201).
    Sorafenib impurity 3
  • HY-Z4481
    Sorafenib impurity 4

    		Drug Intermediate Others
    Sorafenib impurity 4 is an impurity of Sorafenib (HY-10201).
    Sorafenib impurity 4
  • HY-W107225
    Sorafenib impurity 6

    		Drug Intermediate Others
    Sorafenib impurity 6 is an impurity of Sorafenib (HY-10201).
    Sorafenib impurity 6
  • HY-Z3477
    Sorafenib impurity 5

    		Drug Intermediate Others
    Sorafenib impurity 5 is an impurity of Sorafenib (HY-10201).
    Sorafenib impurity 5
  • HY-10201A
    Sorafenib tosylate
    Maximum Cited Publications
    260 Publications Verification

    Bay 43-9006 tosylate

    		 Raf VEGFR FLT3 Autophagy Ferroptosis Apoptosis Cancer
    Sorafenib tosylate (Bay 43-9006 tosylate) is a potent and orally active Raf inhibitor with IC50s of 6 nM and 20 nM for Raf-1 and B-Raf, respectively. Sorafenib tosylate is a multikinase inhibitor with IC50s of 90 nM, 15 nM, 20 nM, 57 nM and 58 nM for VEGFR2, VEGFR3, PDGFRβ, FLT3 and c-Kit, respectively. Sorafenib tosylate induces autophagy and apoptosis. Sorafenib tosylate has anti-tumor activity. Sorafenib tosylate is a ferroptosis activator .
    Sorafenib tosylate
  • HY-10201R
    Sorafenib (Standard)

    Bay 43-9006 (Standard)

    		 Reference Standards Raf VEGFR FLT3 Autophagy Apoptosis Ferroptosis Cancer
    Sorafenib (Standard) is the analytical standard of Sorafenib. This product is intended for research and analytical applications. Sorafenib (Bay 43-9006) is a potent and orally active Raf inhibitor with IC50s of 6 nM and 20 nM for Raf-1 and B-Raf, respectively. Sorafenib is a multikinase inhibitor with IC50s of 90 nM, 15 nM, 20 nM, 57 nM and 58 nM for VEGFR2, VEGFR3, PDGFRβ, FLT3 and c-Kit, respectively. Sorafenib induces autophagy and apoptosis. Sorafenib has anti-tumor activity. Sorafenib is a ferroptosis activator .
    Sorafenib (Standard)
  • HY-133798
    Sorafenib N-oxide

    		Cytochrome P450 Drug Metabolite Cancer
    Sorafenib N-oxide is an active metabolite of sorafenib (HY-10201). Sorafenib N-oxide is a linear-mixed inhibitor of microsomal CYP3A4, with a Ki of 15 μM .
    Sorafenib N-oxide
  • HY-10201AR
    Sorafenib tosylate (Standard)

    Bay 43-9006 tosylate (Standard)

    		 Reference Standards Raf VEGFR FLT3 Autophagy Ferroptosis Apoptosis Cancer
    Sorafenib tosylate (Standard) is the analytical standard of Sorafenib tosylate. This product is intended for research and analytical applications. Sorafenib tosylate (Bay 43-9006 tosylate) is a potent and orally active Raf inhibitor with IC50s of 6 nM and 20 nM for Raf-1 and B-Raf, respectively. Sorafenib tosylate is a multikinase inhibitor with IC50s of 90 nM, 15 nM, 20 nM, 57 nM and 58 nM for VEGFR2, VEGFR3, PDGFRβ, FLT3 and c-Kit, respectively. Sorafenib tosylate induces autophagy and apoptosis. Sorafenib Tosylate has anti-tumor activity. Sorafenib tosylate is a ferroptosis activator .
    Sorafenib tosylate (Standard)
  • HY-W107225R
    Sorafenib impurity 6 (Standard)

    		Reference Standards Drug Intermediate Others
    Sorafenib impurity 6 (Standard) is the analytical standard of Sorafenib impurity 6 (HY-W107225). This product is intended for research and analytical applications.
    Sorafenib impurity 6 (Standard)
  • HY-Z3477R
    Sorafenib impurity 5 (Standard)

    		Reference Standards Drug Intermediate Others
    Sorafenib impurity 5 (Standard) is the analytical standard of Sorafenib impurity 5 (HY-Z3477). This product is intended for research and analytical applications.
    Sorafenib impurity 5 (Standard)
  • HY-10201BR
    Sorafenib impurity 3 (Standard)

    		Reference Standards Drug Intermediate Others
    Sorafenib impurity 3 (Standard) is the analytical standard of Sorafenib impurity 3 (HY-10201B). This product is intended for research and analytical applications.
    Sorafenib impurity 3 (Standard)
  • HY-10201S4
    Sorafenib-d3 tosylate

    Donafenib tosylate; Bay 43-9006-d3 tosylate

    		 Isotope-Labeled Compounds Raf VEGFR FLT3 Autophagy Apoptosis Ferroptosis Cancer
    Sorafenib-d3 (Donafenib-d3) tosylate is the deuterium labeled Sorafenib (HY-10201). Sorafenib is a potent and orally active Raf inhibitor with IC50s of 6 nM and 20 nM for Raf-1 and B-Raf, respectively. Sorafenib-d3tosylate is a multikinase inhibitor with IC50s of 90 nM, 15 nM, 20 nM, 57 nM and 58 nM for VEGFR2, VEGFR3, PDGFRβ, FLT3 and c-Kit, respectively. Sorafenib-d3tosylate induces autophagy and apoptosis. Sorafenib-d3tosylate has anti-tumor activity. Sorafenib is a ferroptosis activator .
    Sorafenib-d3 tosylate
  • HY-10201S1
    Sorafenib-d4

    Bay 43-9006-d4

    		 Raf VEGFR FLT3 Ferroptosis Autophagy Apoptosis Cancer
    Sorafenib-d4 (Bay 43-9006-d4) is the deuterium labeled Sorafenib. Sorafenib is a multikinase inhibitor IC50s of 6 nM, 20 nM, and 22 nM for Raf-1, B-Raf, and VEGFR-3, respectively.
    Sorafenib-d4
  • HY-10201S
    Sorafenib-d3
    1 Publications Verification

    Donafenib; Bay 43-9006-d3

    		 Raf VEGFR FLT3 Ferroptosis Autophagy Apoptosis Cancer
    Sorafenib-d3 (Donafenib), a deuterated compound of Sorafenib, is the first deuterium-generation tumor suppressor small molecule. Sorafenib is a multikinase inhibitor IC50s of 6 nM, 20 nM, and 22 nM for Raf-1, B-Raf, and VEGFR-3, respectively .
    Sorafenib-d3
  • HY-10201S2
    Sorafenib-13C,d3
    1 Publications Verification

    Bay 43-9006-13C,d3

    		 Raf VEGFR FLT3 Autophagy Apoptosis Ferroptosis Cancer
    Sorafenib- 13C,d3 is the 13C- and deuterium labeled Sorafenib. Sorafenib (Bay 43-9006) is a potent and orally active Raf inhibitor with IC50s of 6 nM and 20 nM for Raf-1 and B-Raf, respectively. Sorafenib is a multikinase inhibitor with IC50s of 90 nM, 15 nM, 20 nM, 57 nM and 58 nM for VEGFR2, VEGFR3, PDGFRβ, FLT3 and c-Kit, respectively. Sorafenib induces autophagy and apoptosis. Sorafenib has anti-tumor activity. Sorafenib is a ferroptosis activator .
    Sorafenib-13C,d3
  • HY-W048413R
    Sorafenib impurity 2 (Standard)

    		Reference Standards
    Ethyl (4-chloro-3-(trifluoromethyl)phenyl)carbamate (Standard) is the analytical standard of Ethyl (4-chloro-3-(trifluoromethyl)phenyl)carbamate. This product is intended for research and analytical applications.
    Sorafenib impurity 2 (Standard)
  • HY-123144
    N-Hydroxymethylsorafenib

    		Drug Metabolite Others
    N-Hydroxymethylsorafenib is a Sorafenib (HY-10201) metabolite, and can be used for research of metabolite of Sorafenib .
    N-Hydroxymethylsorafenib
  • HY-173453
    AKR1C3-IN-15

    		Aldose Reductase Apoptosis Cancer
    AKR1C3-IN-15 (compound 30) is a potent and selective AKR1C3 inhibitor with an IC50 of 5 nM. AKR1C3-IN-15 enhances Sorafenib (HY-10201)-induced ROS generation, promoted apoptosis, and restored sorafenib sensitivity in HCC models both in vitro and in vivo .
    AKR1C3-IN-15
  • HY-108226
    Regorafenib N-oxide and N-desmethyl (M5)

    N-Desmethyl regorafenib N-oxide

    		 Drug Metabolite Raf VEGFR c-Kit Cancer
    Regorafenib N-oxide and N-desmethyl (M5) (N-Desmethyl regorafenib N-oxide) is an active metabolite of Sorafenib (HY-10201) and can be metabolized by CYP3A4 .
    Regorafenib N-oxide and N-desmethyl (M5)
  • HY-155248
    HL23

    		HDAC Cancer
    HL23 is a histone deacetylase (HDAC) inhibitor with activity against hepatocellular carcinoma (HCC). HL23 enhances acetylation of the TXNIP promoter and upregulates TXNIP expression, thereby mediating potassium channel activity and triggering TXNIP-dependent potassium deprivation. HL23 inhibits HCC progression and metastasis and has a synergistic effect with Sorafenib (HY-10201) and is more potent than Sorafenib+Vorinostat (HY-10221) .
    HL23
  • HY-112780
    UC2288
    5+ Cited Publications

    		 MDM-2/p53 Apoptosis Cancer
    UC2288 is a potent and orally active p21 attenuator (relatively selective activity for p21), which is synthesized based Sorafenib (HY-10201). UC2288 potently inhibits cancer cell growth by inducing apoptosis. UC2288 has no inhibition of VEGFR2 and Raf kinases even at 10 μM .
    UC2288
  • HY-117720
    OSU-2S

    		PKC Apoptosis Cancer
    OSU-2S is a potent PKCδ activator. OSU-2S inhibits cell proliferation and migration. OSU-2S decreases the expression of p-ERK1/2, increases the expression of PKCδ (38 kDa) when combined with Sorafenib (HY-10201). OSU-2S induces Apoptosis. OSU-2S slao is a non-immunosuppressive analogue of FTY720. OSU-2S shows anticancer activity .
    OSU-2S
  • HY-106856
    Dimiracetam

    NT-11624

    		 iGluR Cancer
    Dimiracetam is an orally active compound, with anti-neuropathic activity. Dimiracetam inhibits hypersensitivity and neurological alterations, and inhibits Sorafenib (HY-10201)-induced neuropathy in cold stimulation rat models .
    Dimiracetam
  • HY-136657
    SC-43
    4 Publications Verification

    		 SHP1 Phosphatase STAT Apoptosis Cancer
    SC-43, a Sorafenib derivative, is a potent and orally active SHP-1 (PTPN6) agonist. SC-43 inhibits the phosphorylation of STAT3 and induces cell apoptosis. SC-43 has anti-fibrotic and anticancer effects .
    SC-43
  • HY-N8439
    Questiomycin A

    Phx-3

    		 HSP Bacterial Antibiotic Infection Cancer
    Questiomycin A (Phx-3) is a GRP78 (cytoprotective endoplasmic reticulum chaperone) degrader and enhances the anticancer activity of Sorafenib. Questiomycin A is also an antimicrobial/antibiotic that can be obtained from the metabolite of Pseudomonas chlororaphis HT66. Questiomycin A can be used in research on biological control of cancer and plant diseases .
    Questiomycin A
  • HY-136658
    STAT3-IN-48
    1 Publications Verification

    		 STAT Apoptosis Cancer
    STAT3-IN-48 is a Sorafenib analogue and potently inhibits the phosphorylation of STAT3. STAT3-IN-48 induces cell apoptosis through SHP-1 dependent STAT3 inactivation. STAT3-IN-48 does not inhibit kinase activity and has anticancer effects .
    STAT3-IN-48
  • HY-133119
    PK150

    		Bacterial Infection
    PK150, an analogue of Sorafenib, shows oral bioavailability and antibacterial activity against several pathogenic strains at submicromolar concentrations. PK150 inhibits Gram-positive Methicillin-sensitive S. aureus (MSSA), Methicillin-resistant S. aureus (MRSA), Vancomycin intermediate S. aureus (VISA) with MICs of 0.3, 0.3-1, 0.3 μM, respectively .
    PK150
  • HY-161284
    MMP-9/10-IN-1

    		MMP Cancer
    MMP-9/10-IN-1 (Compound 6b) is a potent dual MMP-9/10 Inhibotor with IC50s of 0.076 and 0.139 μM against NSCLC and A549 cells, respectively. MMP-9/10-IN-1 has anti-invasive and anti-angiogenic activities when in combination with Sorafenib (HY-10201) .
    MMP-9/10-IN-1
  • HY-174240
    Anticancer agent 274

    		Drug Derivative Cancer
    Anticancer agent 274 (Compound 1) is a Sorafenib (HY-10201) analog. Anticancer agent 274 can inhibit the growth of tumor cells, with IC50 values of 0.034 μM and 0.042 μM against SaOS-2 and MNNG-HOS cells, respectively. Anticancer agent 274 has relatively low toxicity to normal cells and can be used in the research of tumors such as osteosarcoma .
    Anticancer agent 274
  • HY-162934
    TFCP2L1-IN-1

    		Apoptosis Connective Peptide Cancer
    TFCP2L1-IN-1 is a specific small molecule targeting TFCP2L1’s active domain with anti-cancer activity. TFCP2L1-IN-1 synergizes with Sorafenib (HY-10201) to induce Apoptosis and reduces cell proliferation, invasion, metastasis, clonal formation and sphere-forming capacity in hepatocellular carcinoma cells .
    TFCP2L1-IN-1
  • HY-161285
    MMP-9/10-IN-2

    		MMP Cancer
    MMP-9/10-IN-2 (compound 6e) is a potent inhibitor of MMP10 and MMP9, with IC50 of 0.076 μM for MMP10, and 93.18% inhibition at 0.5 μM for MMP9. MMP-9/10-IN-2 plays an important role in anti-tumor .
    MMP-9/10-IN-2
  • HY-W709612
    Regorafenib N-oxide and N-desmethyl (M5)-d3-1

    N-Desmethyl regorafenib N-oxide-d3-1

    		 Isotope-Labeled Compounds VEGFR Raf c-Kit Drug Metabolite Cancer
    Regorafenib N-oxide and N-desmethyl (M5)-d3-1 (N-Desmethyl regorafenib N-oxide-d3-1) is the deuterium labeled Regorafenib N-oxide and N-desmethyl (M5) (HY-108226). Regorafenib N-oxide and N-desmethyl (M5) (N-Desmethyl regorafenib N-oxide) is an active metabolite of Sorafenib (HY-10201) and can be metabolized by CYP3A4 .
    Regorafenib N-oxide and N-desmethyl (M5)-d3-1
  • HY-145723A
    MAX-40279 hydrochloride

    		FLT3 FGFR Inflammation/Immunology Cancer
    MAX-40279 hydrochloride is a dual and orally active inhibitor of FLT3 kinase and FGFR kinase. MAX-40279 hydrochloride is also effective against the FLT3 mutants such as FLT3 D835Y, suggesting that it can overcome resistance to Quizartinib (HY-13001) and Sorafenib (HY-10201). MAX-40279 hydrochloride inhibits NDRG1 phosphorylation at Ser330 and suppresses endothelial-to-mesenchymal transition (EndMT). MAX-40279 hydrochloride can be used for the research of acute myelogenous leukemia (AML) .
    MAX-40279 hydrochloride
  • HY-145723
    MAX-40279
    1 Publications Verification

    		 FLT3 FGFR Inflammation/Immunology Cancer
    MAX-40279 is a dual and orally active inhibitor of FLT3 kinase and FGFR kinase. MAX-40279 is also effective against the FLT3 mutants such as FLT3 D835Y, suggesting that it can overcome resistance to Quizartinib (HY-13001) and Sorafenib (HY-10201). MAX-40279 inhibits NDRG1 phosphorylation at Ser330 and suppresses endothelial-to-mesenchymal transition (EndMT). MAX-40279 can be used for the research of acute myelogenous leukemia (AML) .
    MAX-40279
  • HY-145723C
    MAX-40279 hemiadipate
    1 Publications Verification

    		 FLT3 FGFR Inflammation/Immunology Cancer
    MAX-40279 hemiadipate is a dual and orally active inhibitor of FLT3 kinase and FGFR kinase. MAX-40279 hemiadipate is also effective against the FLT3 mutants such as FLT3 D835Y, suggesting that it can overcome resistance to Quizartinib (HY-13001) and Sorafenib (HY-10201). MAX-40279 hemiadipate inhibits NDRG1 phosphorylation at Ser330 and suppresses endothelial-to-mesenchymal transition (EndMT). MAX-40279 hemiadipate can be used for the research of acute myelogenous leukemia (AML) .
    MAX-40279 hemiadipate
  • HY-145723B
    MAX-40279 hemifumarate
    1 Publications Verification

    		 FLT3 FGFR Inflammation/Immunology Cancer
    MAX-40279 hemifumarate is a dual and orally active inhibitor of FLT3 kinase and FGFR kinase. MAX-40279 hemifumarate is also effective against the FLT3 mutants such as FLT3 D835Y, suggesting that it can overcome resistance to Quizartinib (HY-13001) and Sorafenib (HY-10201). MAX-40279 hemifumarate inhibits NDRG1 phosphorylation at Ser330 and suppresses endothelial-to-mesenchymal transition (EndMT). MAX-40279 hemifumarate can be used for the research of acute myelogenous leukemia (AML) .
    MAX-40279 hemifumarate
  • HY-173393
    LXRα agonist 1

    		LXR Cancer
    LXRα agonist 1 (Compound 40) is a selective LXRα agonist (EC50: 42 nM). LXRα agonist 1 also has a certain agonistic effect on LXRβ (EC50: 266 nM). LXRα agonist 1 promotes target gene transcription by stabilizing the ligand binding domain (LBD) of LXRα. LXRα agonist 1 exhibits potent antitumor effects in hepatocellular carcinoma cells when combined with the Raf inhibitor Sorafenib (HY-10201). LXRα agonist 1 can be used in the study of lipotoxic cancers .
    LXRα agonist 1
  • HY-143303
    Anticancer agent 32

    		Apoptosis Cancer
    Anticancer agent 32 (compound 2g) is an anticancer agent. Anticancer agent 32 shows anticancer activities, affects cell cycle and induces cell apoptosis. Anticancer agent 32 can be used for the research of cancer .
    Anticancer agent 32
  • HY-151458
    VEGFR-2/DHFR-IN-1

    		VEGFR Bacterial Dihydrofolate reductase (DHFR) Fungal Infection Cancer
    VEGFR-2/DHFR-IN-1 (compound 8b) is an inhibitor of VEGFR-2 and DHFR with IC50s of 0.384 and 7.881 μM, respectively. VEGFR-2/DHFR-IN-1 shows good antibacterial activities against Escherichia coli, Streptococcus faecalis, Salmonella enterica, MSSA and MRSA with MIC values of 16, 16, 16, 8, and 16 μg/mL, respectively. VEGFR-2/DHFR-IN-1 exhibits good cytotoxic activities against C26, HepG2, and MCF7 cancer cell lines with IC50 values of 2.97-7.12 μM. VEGFR-2/DHFR-IN-1 can be used for the research of cancer .
    VEGFR-2/DHFR-IN-1
  • HY-151459
    VEGFR-2/DHFR-IN-2

    		VEGFR Bacterial Dihydrofolate reductase (DHFR) Fungal Infection Cancer
    VEGFR-2/DHFR-IN-2 (compound 5b) is an inhibitor of VEGFR-2 and DHFR with IC50s of 0.623 and 9.085 μM, respectively. VEGFR-2/DHFR-IN-2 exhibits good cytotoxic activities against C26, HepG2, and MCF7 cancer cell lines with IC50 values of 3.59-8.38 μM. VEGFR-2/DHFR-IN-2 can be used for the research of cancer .
    VEGFR-2/DHFR-IN-2
  • HY-151624
    PARP-2-IN-2

    		PARP Apoptosis Cancer
    PARP-2-IN-2 (compound 27) is a PARP 2 inhibitor with an IC50 value of 0.057 μM. PARP-2-IN-2 induces cell cycle arrest and apoptosis of MCF-7 breast cancer cells. PARP-2-IN-2 can be used for the research of cancer .
    PARP-2-IN-2
  • HY-123931
    ZLDI-8
    1 Publications Verification

    		 Notch Phosphatase Apoptosis Cancer
    ZLDI-8 is a Notch activating/cleaving enzyme ADAM-17 inhibitor and inhibits the cleavage of Notch protein. ZLDI-8 decreases the expression of pro-survival/anti-apoptosis and epithelial-mesenchymal transition (EMT) related proteins. ZLDI-8 is also a competitive and irreversible tyrosine phosphatase (Lyp) inhibitor with an IC50 of 31.6 μM and a Ki of 26.22 μM. ZLDI-8 inhibits the growth of MHCC97-H cells with an IC50 of 5.32 μM .
    ZLDI-8
  • HY-175646
    AGPAT4-IN-1

    		Acyltransferase mTOR Ribosomal S6 Kinase (RSK) Apoptosis Cancer
    AGPAT4-IN-1 (Compound CL26) is a covalent AGPAT4 inhibitor with an IC50 of 795 nM. AGPAT4-IN-1 covalently binds to AGPAT4 at Cys 228 and significantly inhibits acyltransferase activity, LPA-to-PA conversion and downstream mTOR/S6K pathways. AGPAT4-IN-1 sensitizes hepatocellular carcinoma (HCC) tumors to Sorafenib (HY-10201) and significantly induces apoptosis with a synergistic response. AGPAT4-IN-1 has antitumor activity and reduces tumorigenicity and stemness in HCC xenograft mouse models .
    AGPAT4-IN-1
  • HY-173365
    VEGFR-2-IN-67

    		VEGFR Cancer
    VEGFR-2-IN-67 (Compound 6b) is an inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2). Its IC50 values for MDA-231 and MCF-7 cell lines are 5.91 µM and 7.16 µM respectively, and its inhibitory effect on VEGFR-2 is comparable to that of Sorafenib (HY-10201) (IC50 is 53.63 nM). VEGFR-2-IN-67 exerts significant anti-cancer activity through mechanisms such as inducing Apoptosis (the early apoptosis rate reaches 57.20%), arresting the cell cycle at the G1 phase, upregulating pro-apoptotic markers and downregulating Bcl-2. VEGFR-2-IN-67 can be used for research in the field of cancer .
    VEGFR-2-IN-67
  • HY-119618
    R1498

    		Endogenous Metabolite Cancer
    R1498 is a multi-target kinase inhibitor with anti-angiogenic and anti-proliferative activities. R1498 mainly targets targets such as Aurora kinase and VEGFR2, which are associated with tumor development. R1498 showed moderate in vitro growth inhibition in a variety of tumor cells, with IC50 values in the micromolar range. R1498 showed anti-tumor efficacy superior to sorafenib in a variety of gastric cancer and hepatocellular carcinoma xenograft models, with tumor growth inhibition rates exceeding 80%, and tumor shrinkage was observed in some models. R1498 showed a 10-30% tumor shrinkage rate in three xenograft models derived from human primary gastric cancer tumors, further demonstrating its inhibitory potential. R1498 effectively inhibited Aurora A activity in vivo and reduced tumor vascularization .
    R1498

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