NPASS Compound

Natural Product: NPC477294

Natural Product ID	NPC477294
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Pubescenoside B
IUPAC Name	[3-(hydroxymethyl)-1-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxybut-3-en-2-yl] (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Synonyms	pubescenoside B
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	11464887
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0001766] Fatty acyl glycosides [CHEMONTID:0003861] Fatty acyl glycosides of mono- and disaccharides

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 57 58 0 0 0 0 0 0 0 0999 V2000 -0.0445 -3.5292 -1.4526 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5993 -3.0303 -0.4166 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7933 -3.7164 0.1062 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6516 -4.1095 1.4342 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1226 -1.7949 0.2145 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1528 -0.6818 0.1808 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3490 -0.9947 0.7636 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1819 0.1088 0.6578 C 0 0 1 0 0 0 0 0 0 0 0 0 3.6464 0.6214 1.9891 C 0 0 1 0 0 0 0 0 0 0 0 0 4.6314 1.7238 1.7912 C 0 0 2 0 0 0 0 0 0 0 0 0 4.8632 2.1123 0.3722 C 0 0 1 0 0 0 0 0 0 0 0 0 4.8023 0.9918 -0.6040 C 0 0 2 0 0 0 0 0 0 0 0 0 4.3487 -0.2072 -0.0761 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1166 0.7928 -1.3464 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5594 2.0042 -1.8697 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0020 3.1775 0.0337 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8371 1.4306 2.4681 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5043 1.0499 2.6922 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0104 -1.2503 -0.4267 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1459 -0.9864 0.2931 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1281 -1.2455 1.5140 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3496 -0.4126 -0.3652 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4169 -0.1676 0.3264 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6095 0.3909 -0.2774 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7244 0.6284 0.5360 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9031 1.1566 0.0538 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0316 1.4789 -1.2804 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9542 1.2547 -2.0920 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7679 0.7218 -1.6003 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2354 2.0119 -1.7416 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.0010 1.3842 0.8849 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2951 -4.4477 -1.9318 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9287 -3.0816 -1.8921 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7428 -3.1417 -0.0294 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9548 -4.6420 -0.5141 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7933 -4.6283 1.4819 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1305 -1.9259 1.2908 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6585 0.2122 0.6207 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3342 -0.4472 -0.8969 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6796 0.9642 0.1329 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0586 -0.2264 2.6105 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2259 2.6295 2.3274 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9012 2.5534 0.3098 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0500 1.2806 -1.3956 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9901 0.1090 -2.2105 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8811 0.3118 -0.6925 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0115 1.8672 -2.7388 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7790 3.7216 0.8260 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5600 1.7369 1.8560 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6063 2.0105 2.9491 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3176 -0.2090 -1.4057 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4109 -0.3895 1.3892 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6328 0.3802 1.5761 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0306 1.4988 -3.1393 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9226 0.5518 -2.2662 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1194 1.4871 -1.6884 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.8683 0.9103 0.6677 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 2 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 12 14 1 0 14 15 1 0 11 16 1 0 10 17 1 0 9 18 1 0 5 19 1 0 19 20 1 0 20 21 2 0 20 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 27 30 1 0 26 31 1 0 13 8 1 0 29 24 1 0 1 32 1 0 1 33 1 0 3 34 1 0 3 35 1 0 4 36 1 0 5 37 1 0 6 38 1 0 6 39 1 0 8 40 1 6 9 41 1 1 10 42 1 1 11 43 1 1 12 44 1 6 14 45 1 0 14 46 1 0 15 47 1 0 16 48 1 0 17 49 1 0 18 50 1 0 22 51 1 0 23 52 1 0 25 53 1 0 28 54 1 0 29 55 1 0 30 56 1 0 31 57 1 0 M END

Standard InCHIKey	NGOIXUCFVRGSAM-RPBBZIPLSA-N
Standard InCHI	InChI=1S/C20H26O11/c1-10(7-21)15(9-29-20-19(28)18(27)17(26)14(8-22)31-20)30-16(25)5-3-11-2-4-12(23)13(24)6-11/h2-6,14-15,17-24,26-28H,1,7-9H2/b5-3+/t14-,15?,17-,18+,19-,20-/m1/s1
SMILES	C=C(CO)C(CO[C@H]1[C@@H]([C@H]([C@@H]([C@H](O1)CO)O)O)O)OC(=O)/C=C/C2=CC(=C(C=C2)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	442.15	Volume:	418.237 ? Van der Waals volume.
Dense:	1.057	LogP:	-0.107 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.774 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.23 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	15.0
TPSA:	186.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	7.0	Rings:	2.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.101	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.331	Fsp³:	0.45
MCE-18:	56.862 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.603	Fluc inhibitor:	0.571 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.059 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.439 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.286	Promiscuous compounds:	0.216

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.098	MDCK Permeability:	-5.204
Pgp-inhibitor:	0.0	Pgp-substrate:	0.057
PAMPA:	0.988 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.909
20% Bioavailability (F20%):	0.949	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.007	MRP1:	0.024
Plasma Protein Binding (PPB):	64.18%	Volume Distribution (VD):	-0.403
Fu:	35.446% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.014
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.205
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.579
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.983
HLM stability:	0.442 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

4.666

Half-life (T1/2):

2.074

ADMET: Toxicity

hERG Blockers:	0.014	hERG Blockers (10um):	0.086
Human Hepatotoxicity (H-HT):	0.676	Drug-induced Liver Injury (DILI):	0.66
AMES Toxicity:	0.938	Rat Oral Acute Toxicity:	0.008
Maximum Recommended Daily Dose:	0.051	Skin Sensitization:	1.0
Carcinogencity:	0.266	Eye Corrosion:	0.0
Eye Irritation:	0.44	Respiratory Toxicity:	0.004
Drug-induced Neurotoxicity:	0.017	Ototoxicity:	0.975
Hematotoxicity:	0.103	Drug-induced Nephrotoxicity:	0.475
Genotoxicity:	0.412	RPMI-8226 Immunitoxicity:	0.031
A549 Cytotoxicity:	0.466	Hek293 Cytotoxicity:	0.215
BCF:	0.435 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.171 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.025 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.133 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO14547	Ilex pubescens	Species	Aquifoliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15787443]
NPO14547	Ilex pubescens	Species	Aquifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14547	Ilex pubescens	Species	Aquifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14547	Ilex pubescens	Species	Aquifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14547	Ilex pubescens	Species	Aquifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
Activity	1

Activity Type	# Activity
Organism	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT29	Organism	Rattus norvegicus	Rattus norvegicus	Activity	=	27.3	%	PMID[15787443]

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC477294 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	12082
0.1-0.2	31736
0.2-0.3	4706
0.3-0.4	1046
0.4-0.5	230
0.5-0.6	51
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.7059	Intermediate Similarity	NPC477293
0.7049	Intermediate Similarity	NPC232880
0.6094	Remote Similarity	NPC11724
0.5942	Remote Similarity	NPC52097
0.5833	Remote Similarity	NPC476376
0.5823	Remote Similarity	NPC476867
0.5814	Remote Similarity	NPC298257
0.5814	Remote Similarity	NPC175214
0.5692	Remote Similarity	NPC313193
0.5676	Remote Similarity	NPC229784
0.5663	Remote Similarity	NPC475484
0.5616	Remote Similarity	NPC470572
0.56	Remote Similarity	NPC473924
0.557	Remote Similarity	NPC225307
0.5568	Remote Similarity	NPC119537
0.5556	Remote Similarity	NPC476864
0.5513	Remote Similarity	NPC219677
0.5435	Remote Similarity	NPC476375
0.5435	Remote Similarity	NPC476384
0.5432	Remote Similarity	NPC28637
0.5422	Remote Similarity	NPC18789
0.5422	Remote Similarity	NPC205195
0.5422	Remote Similarity	NPC476868
0.5395	Remote Similarity	NPC186406
0.5395	Remote Similarity	NPC886
0.5395	Remote Similarity	NPC287597
0.5385	Remote Similarity	NPC473285
0.5366	Remote Similarity	NPC220942
0.5366	Remote Similarity	NPC81515
0.5319	Remote Similarity	NPC476381
0.5312	Remote Similarity	NPC224208
0.5312	Remote Similarity	NPC41661
0.5294	Remote Similarity	NPC222433
0.5294	Remote Similarity	NPC12006
0.5294	Remote Similarity	NPC486495
0.5278	Remote Similarity	NPC157554
0.5233	Remote Similarity	NPC76406
0.5208	Remote Similarity	NPC64195
0.5181	Remote Similarity	NPC260425
0.5176	Remote Similarity	NPC472350
0.5176	Remote Similarity	NPC197316
0.5176	Remote Similarity	NPC89105
0.5158	Remote Similarity	NPC476380
0.5158	Remote Similarity	NPC476378
0.5135	Remote Similarity	NPC202700
0.5119	Remote Similarity	NPC476866
0.5116	Remote Similarity	NPC31745
0.5116	Remote Similarity	NPC134405
0.5116	Remote Similarity	NPC220936
0.5077	Remote Similarity	NPC474275
0.5075	Remote Similarity	NPC65791
0.5068	Remote Similarity	NPC307110
0.5063	Remote Similarity	NPC34293
0.5062	Remote Similarity	NPC292443

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC477294 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5024
0.1-0.2	4013
0.2-0.3	104
0.3-0.4	7
0.4-0.5	1
0.5-0.6	1
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.5176	Remote Similarity	NPD7266	Phase 2

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data