- Chemical generation of small molecule-based bispecific antibody-drug conjugates for broadening the target scope
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Antibody-drug conjugates (ADCs) hold great therapeutic promise for cancer indications; however, treating tumors with intratumor heterogeneity remains challenging. We hypothesized that ADCs that can simultaneously target two different cancer antigens could
- Yamaguchi, Aiko,Anami, Yasuaki,Ha, Summer Y.Y.,Roeder, Travis J.,Xiong, Wei,Lee, Jangsoon,Ueno, Naoto T.,Zhang, Ningyan,An, Zhiqiang,Tsuchikama, Kyoji
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- Synthesis and anti-cancer evaluation of folic acid-peptide- paclitaxel conjugates for addressing drug resistance
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The drug resistance and the poor water solubility are major limitations of paclitaxel (PTX) of based chemotherapy. To conquer the two problems, targeting folate (FA) receptor PTX-lytic peptides conjugates were synthesized and evaluated. Compared with PTX, FA-P3-PTX and FA-P7-PTX displayed significantly enhanced cell toxicity in many cancer cells, particularly drug resistant cancer cells MCF-7/PTX. FA-P7-PTX possessed stronger effect on cell toxicity (IC50 = 2.92 ± 0.2 μM), membrane disrupting activity and pro-apoptosis in MCF-7/PTX cells than FA-P3-PTX. Further investigation displayed that the anti-cancer mechanisms of FA-P3-PTX and FA-P7-PTX might be a mitochondrial impairment and caspase-3-dependent apoptotic cell death. Furthermore, the in vivo antitumor efficacy study confirmed that FA-P7-PTX performed more stronger potency in inhibition of tumors growth than PTX. The study demonstrated that conjugate FA-P7-PTX with superior properties for antineoplastic activity, which makes it a promising potential candidate for drug-resistant cancer therapy.
- Dai, Yuxuan,Cai, Xingguang,Bi, Xinzhou,Liu, Chunxia,Yue, Na,Zhu, Ying,Zhou, Jiaqi,Fu, Mian,Huang, Wenlong,Qian, Hai
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- USES OF ANTI-CD3 ANTIBODY FOLATE BIOCONJUGATES
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Described herein are anti-CD3 antibody folate bioconjugates and uses thereof in the treatment of diseases, conditions, and cancers.
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Paragraph 00347; 00348
(2021/09/03)
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- Preparation method of N10-trifluoroacetyl pteroic acid
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The invention provides a preparation method of N10-trifluoroacetyl pteroic acid. The preparation method comprises the following step: reacting a compound trifluoroacetic acid or trifluoroacetic anhydride or a mixed solution of the trifluoroacetic acid and the trifluoroacetic anhydride with instant pteroic acid or a mixture of the instant pteroic acid and anhydrous pteroic acid in a DMSO or DMF solvent to obtain the N10-trifluoroacetyl pteroic acid. The method is simple in process, trifluoroacetic anhydride is prevented from being used as a solvent, the reaction time is greatly shortened, and industrial production is facilitated.
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Paragraph 0022-0027
(2021/10/05)
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- ANTI-CD3 ANTIBODY FOLATE BIOCONJUGATES AND THEIR USES
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Described herein are novel anti-CD3 Folate antibodies and uses thereof in the treatment of diseases or conditions that would benefit from such.
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Paragraph 00338-00340
(2020/03/23)
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- FOLATE DERIVATIVES, USEFUL IN PARTICULAR IN THE CONTEXT OF THE FOLATE ASSAY
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Use of a folate derivative to assay in vitro the folate in a sample such as a biological sample.
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Paragraph 0236
(2018/07/05)
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- Riboflavin-targeted polymer conjugates for breast tumor delivery
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Purpose: In breast cancer, a significant decrease in riboflavin (RF) serum levels and increase in RF carrier protein occurs, indicating a potential role of RF in disease progression. To evaluate RF's ability to serve as a targeting agent, mitomycin C (MMC)-conjugated N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers were synthesized and targeted to the RF internalization pathway in human breast cancer cells. Methods: Competitive uptake studies were used to determine specificity of RF-targeted conjugates, and an MTT assay established the IC50 for the conjugates. Endocytic mechanisms were investigated by confocal microscopy. Results: Studies revealed a high-affinity endocytic mechanism for RF-specific internalization of fluorescently-labeled conjugates in both MCF-7 and SKBR-3 cells, whereas folic acid-mediated endocytosis showed high specificity only in SKBR-3 cells. MMC internalization was significantly higher following nontargeted and RF-targeted MMC-conjugate administration compared to that of free MMC. Cytotoxic analysis illustrated potent IC 50 values for RF-targeted MMC conjugates similar to free MMC. Maximum nuclear accumulation of MMC resulted from lysosomal release from RF-targeted and nontargeted MMC-conjugates following 6 h incubations, unlike that of free MMC seen within 10 min. Conclusion: Targeting polymer-MMC conjugates to the RF internalization pathway in breast cancer cells enabled an increase in MMC uptake and nuclear localization, resulting in potent cytotoxic activity.
- Bareford, Lisa M.,Avaritt, Brittany R.,Ghandehari, Hamidreza,Nan, Anjan,Swaan, Peter W.
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p. 1799 - 1812
(2013/07/19)
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- PROCESSES FOR MAKING EPOTHILONE COMPOUNDS AND ANALOGS
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The present invention relates to processes for making epothilone compounds and analogs thereof, such as epi-epothilone A or epi-epothilone B, and aziridinyl-epothilone analogs.
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Page/Page column 47-48
(2009/01/20)
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- POSITRON EMISSION TOMOGRAPHY IMAGING METHOD
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Described herein are compositions and methods for diagnosing and/or monitoring pathogenic disease states using positron emission tomography, wherein the pathogenic cells uniquely express, preferentially express, or overexpress vitamin receptors. Also described herein are 18F conjugates of vitamins and vitamin receptor- binding analogs and derivatives.
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Page/Page column 30-31
(2008/12/08)
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- AZIRIDINYL-EPOTHILONE COMPOUNDS
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The present invention is directed to aziridinyl epothilone compounds as further described herein, and/or pharmaceutically-acceptable salts and/or solvates thereof having the following Formula: wherein K is —O—, —S—, or —NR7—; A is —(CR8R9)—(CH2)m-Z- wherein Z is —(CHR10)—, —C(═O)—, —C(═O)—C(═O)—, —OC(═O)—, —N(R11)C(═O)—, —SO2—, or —N(R11)SO2—; B1 is hydroxyl or cyano and R1 is hydrogen or B1 and R1 are taken together to form a double bond; R2, R3, and R5 are, independently, hydrogen, alkyl, substituted alkyl, aryl or substituted aryl; or R2 and R3 may be taken together with the carbon to which they are attached to form an optionally substituted cycloalkyl; R4 is hydrogen, alkyl, alkenyl, substituted alkyl, substituted alkenyl, aryl, or substituted aryl; R6 is hydrogen, alkyl or substituted alkyl; R7, R8, R9, R10, R11 and R12 are independently hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heterocycloalkyl, substituted heterocycloalkyl, heteroaryl, or substituted heteroaryl; and R13 is aryl, substituted aryl, heteroaryl or substituted heteroaryl.
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- Chemiluminescence quenching of pteroic acid-N-sulfonyl-acridinium-9- carboxamide conjugates by folate binding protein
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N10-Trifluoroacetylpteroic acid was conjugated to chemiluminescent N-sulfonylacridinium-9-carboxamide labels at the N10 or 9-position carboxamide. Upon binding to folate binding protein the light output of the N10 derivative (9) was quenched up to 62% upon triggering with basic peroxide, while the 9-position carboxamide conjugate (7) was quenched only 12%. The utility of this effect was demonstrated in a model homogeneous chemiluminescent assay for folic acid.
- Adamczyk, Maciej,Fino, James R.,Mattingly, Phillip G.,Moore, Jeffrey A.,Pan, You
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p. 2313 - 2317
(2007/10/03)
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- Efficient syntheses of pyrofolic acid and pteroyl azide, reagents for the production of carboxyl-differentiated derivatives of folic acid
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Reaction of folic acid (1) with excess trifluoroacetic anhydride provides access to both the previously unknown N10-(trifluoroacetyl)pyrrofolic acid (8) and pyrofolic acid (9). Reaction of either of these materials with hydrazine selectively affords pteroyl hydrazide (13), which may be oxidized to pteroyl azide (27) on a large scale (62% overall from I without the need for chromatography). Treatment of 27 with differentially protected glutamates provides a convenient and high-yielding synthesis of differentially protected, optically pure folates.
- Luo, Jin,Smith, Michael D.,Lantrip, Douglas A.,Wang, Susan,Fuchs
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p. 10004 - 10013
(2007/10/03)
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