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1 receptor agonist) was a blood-brain barrier penetrant.
2 steosarcoma development, which remained 100% penetrant.
3 nducing peptides that are intrinsically cell-penetrant.
4 of agonist 4-fold, and the racemate is brain-penetrant.
5 as a means for rendering peptides more cell-penetrant.
6 Blebb was found to be highly brain penetrant.
7 ide range of mental disorders and are highly penetrant.
8 cases are underdiagnosed and/or incompletely penetrant.
9 ein] and is autosomal dominant and partially penetrant.
10 background but are unlikely to be completely penetrant.
11 ffected by diet and several are incompletely penetrant.
12 LK2 which are orally bio-available and brain-penetrant.
13 types, including those that are incompletely penetrant (2), automated identification of causative mut
14 , from birth resulted in spontaneous, highly penetrant AD with many of the major hallmarks of human A
15 harmacokinetics study, compound 9t was brain-penetrant after oral dosing, but exposure was limited by
16 the point of being permeable to normally non-penetrant agents without causing significant acute damag
17 a novel, highly potent, selective, and brain-penetrant ALK and ROS1 TKI with preclinical activity aga
19 t, selective, orally bioavailable, and brain-penetrant ALK2 inhibitors based on the lead compound LDN
24 ozygous human mutations of NKX2-5 are highly penetrant and associated with varied congenital heart de
25 he rapid development of an aggressive, fully-penetrant and cell-autonomous myeloid leukaemia in mice,
26 11.2 deletion syndrome (22q11DS) is a highly penetrant and common genetic cause of neuropsychiatric d
30 er, telomerase variants are not always fully penetrant and in some families disease-causing variants
32 d i.c.v. administrations of SR11935, a brain-penetrant and JNK2/3 isoform-selective inhibitor, exerte
35 d with the disease, most of which are highly penetrant and often cause early onset or atypical sympto
36 ction of NB-360, a novel blood-brain barrier penetrant and orally available BACE1 inhibitor, was veri
38 of 14 (PF-06447475), a highly potent, brain penetrant and selective LRRK2 inhibitor which has been f
39 (i.c.v.) administration of SR-3306, a brain-penetrant and selective pan-JNK (JNK1/2/3) inhibitor, re
40 fication of new 1,4-benzodiazepines as brain penetrant and selective triple T-type calcium channel bl
44 rms for the logP and molecular weight of the penetrant and the refractive index of the vehicle mixtur
45 was developed to describe the effects of the penetrant and vehicle mixture properties on the mean dif
48 or suppressor gene, and they provide a fully penetrant animal model for the study of angiosarcoma dev
49 28-day treatment with S 38093, a novel brain-penetrant antagonist/inverse agonist of H3 receptors, on
50 ctivation, and this is alleviated by the CNS-penetrant antioxidant, indapamide.SIGNIFICANCE STATEMENT
52 ans, the beta2AR agonist salbutamol, a brain-penetrant asthma medication, was associated with reduced
53 rmline variants were found in the moderately penetrant ATM and CHEK2 genes, where only truncating var
56 PF-06463922, a novel, orally available, CNS-penetrant, ATP-competitive small-molecule inhibitor of A
58 primary torsion dystonia (AOPTD) is a poorly penetrant autosomal dominant disorder; most gene carrier
61 nvestigated the effects of a potent nonbrain-penetrant BACE1 inhibitor, delivered directly to the bra
63 (Gt-ex13) heterozygotes exhibit incompletely penetrant BAV, CoA and PDA phenotypes similar to those i
64 explain aberrant structural connectivity and penetrant behavioral consequences in mice as well as hum
67 poietic system, which phenocopied the highly penetrant bone marrow failure seen in Fanconi anaemia pa
68 potent (mGlu1 EC50 = 31.8 nM) and highly CNS penetrant (brain to plasma ratio (Kp) of 1.02) mGlu1 PAM
69 .4) variant associated with diabetes is <10% penetrant by the time an individual is 40 years old.
70 ort can enhance the overall permeance of the penetrant by up to an order of magnitude, but this gain
71 d the in vivo efficacy of nilotinib, a brain penetrant c-Abl inhibitor, in the acute MPTP-induced mod
73 gets in Li-Fraumeni syndrome (LFS), a highly penetrant cancer predisposition syndrome associated with
76 We investigate the genetic basis of highly penetrant cancer susceptibility in RF/J finding private
78 , with a large number of distinct and highly penetrant causal variants identified among a growing lis
79 is a relatively common monogenic and highly penetrant cause of autism spectrum disorder (ASD) and in
80 chiatric adverse effects observed with brain-penetrant CB1R blockers, ameliorate obesity and its mult
81 -55 (GSK232), a highly selective, cellularly penetrant CECR2 inhibitor with excellent physicochemical
84 smatch repair deficiency (bMMRD) is a highly penetrant childhood cancer syndrome often resulting in G
85 up15q syndrome is one of the most common and penetrant chromosomal abnormalities observed in individu
86 novel NFKB2 GOF mutations produce a nonfully penetrant CID phenotype through a different pathophysiol
87 distinct from UTX mutation, including fully penetrant cleft palate, mandible hypoplasia and deficits
89 les with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented
90 runcating fat1a mutations exhibit completely penetrant coloboma, recapitulating the most consistent d
91 variability between treatments (vehicle and penetrant combinations) as well as noise within treatmen
92 l-3-pyridincarboxamides, including the brain-penetrant compound 14G: [5-(4-chlorophenyl)-6-(cycloprop
93 esulted in a highly potent, selective, brain penetrant compound 71 (PF-05085727) that effects in vivo
94 nts in genetic analyses, particularly highly penetrant contributors to severe Mendelian disorders.
95 toderm (NNE) and Grhl2 loss results in fully penetrant cranial neural tube defects (NTDs) in mice.
97 l that includes genes associated with highly penetrant CRCP syndromes in addition to Lynch syndrome g
98 genes and other genes associated with highly penetrant CRCP syndromes led to an average increase of 0
99 ated pexacerfont, an orally available, brain penetrant CRH1 antagonist for its ability to suppress st
100 ned and synthesized a highly selective brain-penetrant CSF1R inhibitor (PLX5622) allowing for extende
101 bryos lacking this enhancer display variably penetrant defects in anterior-posterior axis orientation
106 or (GR)50 during development caused a highly penetrant developmental arrest, while post-developmental
107 and infection underlie FSGS; however, highly penetrant disease genes have been identified in a small
108 thmogenic cardiomyopathy (ACM) is a variably penetrant disease increasingly identified in young patie
110 BCL11A erythroid enhancer results in highly penetrant disruption of this motif, reduction of BCL11A
112 nary potential, however, relatively few anti-penetrant drugs have been developed to control fungal di
113 AD, who were affected carriers of the fully penetrant E280A mutation in the presenilin-1 (PSEN1) gen
115 , seip-1 Homozygous seip-1 mutants displayed penetrant embryonic lethality, which is caused by the di
116 c deficiency in mice resulted in a partially penetrant embryonic or perinatal lethal phenotype, with
119 e mutation in titin as the cause of a highly penetrant familial cardiomyopathy with features of left
120 Z1-null mice, although viable, display fully penetrant female-specific lymphoproliferative disorder.
121 ms that are downstream targets of highly ASD-penetrant FMR1 and CHD8 genes are also heavily affected
122 sources in the brain when triggered by brain-penetrant focused ultrasound (FUS) through intact scalp
125 inding domain) missense mutations are highly penetrant for varied congenital heart defects, including
126 els in cells that lack centrioles led to the penetrant formation of de novo centrioles that gained th
128 neage-restricted progenitors to induce fully penetrant GBM using CNS progenitor-specific inducible Cr
136 ed variants in BRCA2 as the most common high-penetrant genetic factor associated with pancreatic canc
137 py number variants are among the most highly penetrant genetic risk variants for developmental neurop
138 igation of neuroimaging biomarkers in highly penetrant genetic syndromes represents a more biological
139 ence can serve as a model to identify highly penetrant genetic variants in closely related individual
140 tudies enable researchers to identify highly penetrant genetic variants too rare to be tested in conv
142 tified the first orally bioavailable and CNS penetrant glucagon-like peptide-1 receptor (GLP-1R) nonc
143 sought to identify structurally novel, brain penetrant, GluN2B-selective inhibitors suitable for eval
144 dings have resulted in an efficacious, brain-penetrant GPR52 agonist as a valuable pharmacological to
146 harbors in-frame exon deletions in partially penetrant hereditary retinoblastomas and is known to imp
148 ferin pairs emit light that is poorly tissue penetrant, hindering efforts to visualize targets in dee
152 cognised functional class that contribute to penetrant human disease, and demonstrate the power of la
153 ery of the highly potent and selective brain-penetrant hV1a antagonist RO5028442 (8) suitable for hum
155 ions in glioma highlights the need for brain-penetrant IDH1 mutant-selective inhibitors as an alterna
156 rst time the effect of a blood-brain barrier-penetrant IMPase inhibitor on human central nervous syst
157 auses embryonic defects, which are partially penetrant in an inbred strain but fully lethal in non-in
161 ately selective, orally available, and brain-penetrant in wild-type mice, and confirmation of target
167 kout mice with a new, highly specific, brain-penetrant inhibitor of MAP kinase-interacting kinases re
168 hat disruption of 2-HG production with brain-penetrant inhibitors in IDH1 mutant gliomas may have sub
170 al and DMPK properties to afford the non-CNS penetrant inverse agonist 22 (AZ-GHS-22) and the CNS pen
172 d a novel series of aryl sulfonamides as CNS-penetrant, isoform-selective Na(V)1.6 inhibitors, which
175 induced myeloid transformation, with a fully penetrant, lethal chronic myelomonocytic leukemia (CMML)
177 Aquaporin 4, EAAT2b), while others are quite penetrant (lipophilic molecules, Cx30, ZO-1, Occludin).
178 t LXR-623, a clinically viable, highly brain-penetrant LXRalpha-partial/LXRbeta-full agonist selectiv
179 low-clearance, orally bioavailable, and CNS-penetrant M1-selective PAM with minimal agonist activity
184 Atoh1 transgene expression developed highly penetrant medulloblastoma at a young age with extensive
185 deletion of Pten and Trp53 resulted in fully penetrant medulloblastoma originating from the perivascu
187 s in this model led to accelerated and fully penetrant melanomagenesis and synchronous tumor formatio
188 illness are not exclusively caused by highly penetrant Mendelian mutations, but can also be contribut
189 covery of a new, orally bioavailable and CNS-penetrant metabotropic glutamate receptor 7 (mGlu(7)) ne
190 murine intestinal epithelium leads to highly penetrant metastasis (100% metastasis; with >80% liver m
192 lecular mechanisms of the most prevalent and penetrant microdeletion associated with neurodevelopment
193 t agonist delivered by a blood-brain barrier penetrant microglia-specific targeting nanocarrier we pr
194 inal epithelium and the effective killing of penetrant microorganisms, while suppressing the activati
197 loinsufficiency of the Shank3 gene (a highly penetrant monogenic autism risk factor), which exhibits
198 domains 3 (SHANK3) gene represents a highly penetrant, monogenic risk factor for autism spectrum dis
200 tly, administration of Epothilone D, a brain-penetrant MT-stabilizing natural product, was found to r
201 y is sufficient for the development of fully-penetrant, multifocal carcinomas, closely mimicking huma
202 nd elucidate mechanisms through which highly penetrant, multigene copy number variants contribute to
204 on because affected individuals, but not non-penetrant mutation carriers, have a greater reduction of
205 ease caused by an autosomal dominant, highly penetrant mutation in the presenilin-1 (PSEN1) gene, and
207 ic disorders - whether caused by rare highly penetrant mutations or sporadic forms - and holds promis
213 d delivers neurotensin, an otherwise non-BBB-penetrant neuropeptide, at levels capable of modulating
214 n CDH1 mutation-positive families, including penetrants, non-penetrants or non-carriers for NSCLP.
215 s regard, we evaluated the effect of a brain-penetrant, novel multifunctional dopamine D2/D3 agonist,
216 entify a significant cellular effect of rare penetrant NRXN1 mutations in human neurons, which was fo
217 ntral motor neurons, resulting in completely penetrant NT defects, while excision after embryonic day
220 orders that are also characterized by highly penetrant obesity, a major additional risk factor, is un
223 CNS targets and classified as either "brain penetrant" or "peripherally restricted" on the basis of
224 eries of highly potent, selective, and brain-penetrant oxazole-4-carboxamide-based inhibitors of glyc
228 per eye compared with those with known high-penetrant pathogenic variants and are more likely to rem
230 autosomal genes as well as into the variably penetrant pathophysiological spectrum of phenotypes obse
231 ceptor-mediated transcytosis using the brain-penetrant peptide Angiopep-2 (An2), which targets LDL re
232 the anterior hypothalamus results in a fully penetrant phenotype characterised by a complete arrest o
234 deletion of ZFP57 in mice presents a highly penetrant phenotype with no animals surviving to birth.
235 oid for Pals1) in nephrons developed a fully penetrant phenotype, characterized by cyst formation and
238 NA loss-of-function rarely results in highly penetrant phenotypes, but rather, influences cellular re
243 Dicer1 (S1836D/S1836D) mice display highly penetrant postnatal lethality, and the few survivors dis
245 isease [KD]), a central nervous system (CNS)-penetrant protective agent rescued myelin and oligodendr
246 dominant-negative) form of a rare but highly penetrant psychiatric risk factor, Disrupted-In-Schizoph
251 eveloped more severe pyelonephritis and 100% penetrant renal abscess (a complication that is rare in
254 utations in established moderately or highly penetrant risk genes for breast cancer (BC) and/or ovari
257 This extreme phenotype likely harbors highly penetrant risk variants, making it primed for discovery
258 essing (Myf5-expressing) cells develop fully penetrant sarcomagenesis, suggesting skeletal muscle pro
259 xplored the impact of one of the most highly penetrant schizophrenia risk genes, DISC1, upon the medi
260 hosphoinositide 3-kinase (PI3K), have highly penetrant secretion of autoreactive IgM antibodies.
262 s neurodegenerative disorder caused by fully penetrant single gene mutations in a minority of cases,
263 ed risk stratification utility of common low penetrant single nucleotide polymorphisms (SNPs) and epi
264 onditional gene targeting to develop a fully penetrant small animal model of this disease that recapi
265 ological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthet
267 ize the discovery of highly selective, brain-penetrant, small molecule p38alphaMAPK inhibitors that a
270 e common risk variants and rarer more highly penetrant submicroscopic chromosomal deletions and dupli
271 tors, although orally bioavailable and brain-penetrant, suffer from unfavorable off-target binding to
272 t disease-causing BMPR2 mutation is only 20% penetrant, suggesting that genetic variation provides mo
274 ng the basis of microcephaly in AS, a highly penetrant syndromic feature with early postnatal onset,
277 h longer half-life and to be much more brain penetrant than SKA-121, not only lowered blood pressure
279 ive on ALK-dependent cell lines, efficiently penetrant the blood-brain barrier (BBB) in different ani
280 source for rational development of new brain-penetrant therapeutics and for advancing understanding o
285 es are nonimmunogenic, are freely and deeply penetrant to human OA cartilage, and persist in chondroc
286 ies of PQR620 (52), the first-in-class brain penetrant TORKi showing efficacy in a TSC mouse model.
288 ence that systemic administration of a brain-penetrant TrkB antagonist (tat-cyclotraxin-B) reduces se
289 show that systemic administration of a brain-penetrant TrkB antagonist leads to brain region-specific
292 al triplications cause a frequent and highly penetrant type of autism linked to increased gene dosage
294 discovery of a potent, selective, and brain-penetrant V1a receptor antagonist, which was not suitabl
295 m of frequency and effect, from rare, highly penetrant variants to common risk alleles with small eff
299 4 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprot