NPASS Compound

Natural Product: NPC506272

Natural Product ID	NPC506272
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5,6-dihydroxy-3-(4-hydroxyphenyl)-8-methoxy-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name	5,6-dihydroxy-3-(4-hydroxyphenyl)-8-methoxy-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 56 59 0 0 0 0 0 0 0 0999 V2000 -0.7603 -2.5606 -1.4698 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3453 -2.3364 -0.1261 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1219 -1.1075 0.2935 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7769 -0.1945 0.7906 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1388 -0.3982 0.9126 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0915 -0.0879 -0.0863 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.8804 0.9715 0.3267 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0969 1.0141 -0.3463 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.7603 2.3579 -0.1809 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9149 3.3357 -0.7013 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9396 -0.1047 0.2271 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.2432 -0.0570 -0.2641 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2487 -1.3964 -0.0557 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.3582 -2.2977 1.0303 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8376 -1.2819 -0.5388 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7721 -1.4386 -1.9339 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2503 1.0316 1.1998 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0982 1.9971 1.7102 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0889 1.3083 1.1104 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6276 2.5188 1.5115 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9445 0.3555 0.6039 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4810 -0.8600 0.1895 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3146 -1.7553 -0.2908 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6063 -1.5269 -0.3924 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1535 -0.3287 0.0027 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5713 -0.0297 -0.0898 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5262 -0.9482 0.3136 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8761 -0.6769 0.2305 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3300 0.5277 -0.2608 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7045 0.8015 -0.3445 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3921 1.4531 -0.6667 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0345 1.1747 -0.5808 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2756 0.6247 0.5126 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7347 1.7279 0.8831 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6069 -3.2694 -1.4717 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1016 -2.9753 -2.0212 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0259 -1.5786 -1.9052 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5015 0.3118 -0.9638 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9440 0.8402 -1.4213 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0140 2.5948 0.8629 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6777 2.3573 -0.8049 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0931 2.9294 -1.0929 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9216 0.0425 1.3458 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7447 -0.7708 0.2292 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8374 -1.8995 -0.8799 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1238 -3.1980 0.6386 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2996 -2.1897 -0.1321 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2780 -0.6559 -2.2839 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2750 2.0214 2.7074 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7989 3.2053 0.7801 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2875 -2.2817 -0.7942 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1879 -1.8970 0.7009 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6368 -1.3935 0.5458 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0408 1.6945 -0.6154 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7414 2.3962 -1.0514 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2781 1.9028 -0.9008 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 8 11 1 0 11 12 1 0 11 13 1 0 13 14 1 0 13 15 1 0 15 16 1 0 4 17 1 0 17 18 1 0 17 19 2 0 19 20 1 0 19 21 1 0 21 22 2 0 22 23 1 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 29 30 1 0 29 31 1 0 31 32 2 0 25 33 1 0 33 34 2 0 22 3 1 0 32 26 1 0 15 6 1 0 33 21 1 0 1 35 1 0 1 36 1 0 1 37 1 0 6 38 1 6 8 39 1 6 9 40 1 0 9 41 1 0 10 42 1 0 11 43 1 1 12 44 1 0 13 45 1 6 14 46 1 0 15 47 1 1 16 48 1 0 18 49 1 0 20 50 1 0 24 51 1 0 27 52 1 0 28 53 1 0 30 54 1 0 31 55 1 0 32 56 1 0 M END

Standard InCHIKey	VWMPPGJQMLFNRK-PQMDEDJFSA-N
Standard InCHI	InChI=1S/C22H22O12/c1-31-21-19-12(13(25)10(7-32-19)8-2-4-9(24)5-3-8)15(27)17(29)20(21)34-22-18(30)16(28)14(26)11(6-23)33-22/h2-5,7,11,14,16,18,22-24,26-30H,6H2,1H3/t11-,14-,16+,18-,22+/m1/s1
SMILES	COC1=C(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)C(O)=C(O)C2=C1OC=C(C1=CC=C(O)C=C1)C2=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	478.11	Volume:	439.233 ? Van der Waals volume.
Dense:	1.089	LogP:	0.062 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.935 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.782 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	24.0
TPSA:	199.51 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.238	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.121	Fsp³:	0.318
MCE-18:	90.31 ? 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:	0.462	Fluc inhibitor:	0.256 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.69 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.724 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.098	Promiscuous compounds:	0.509

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.333	MDCK Permeability:	-5.317
Pgp-inhibitor:	0.0	Pgp-substrate:	0.058
PAMPA:	0.999 ? 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):	0.228
20% Bioavailability (F20%):	0.387	30% Bioavailability (F30%):	0.964
50% Bioavailability (F50%):	0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.036	MRP1:	0.312
Plasma Protein Binding (PPB):	80.967%	Volume Distribution (VD):	-0.102
Fu:	17.751% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.992
OATP1B3 inhibitor:	0.99	BCRP inhibitor:	0.228
BSEP inhibitor:	0.002

ADMET: Metabolism

CYP1A2-inhibitor:	0.021	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.018	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.008
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.824
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.858
HLM stability:	0.021 ? 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):

3.662

Half-life (T1/2):

3.704

ADMET: Toxicity

hERG Blockers:	0.028	hERG Blockers (10um):	0.171
Human Hepatotoxicity (H-HT):	0.698	Drug-induced Liver Injury (DILI):	0.923
AMES Toxicity:	0.73	Rat Oral Acute Toxicity:	0.064
Maximum Recommended Daily Dose:	0.111	Skin Sensitization:	0.993
Carcinogencity:	0.262	Eye Corrosion:	0.0
Eye Irritation:	0.132	Respiratory Toxicity:	0.021
Drug-induced Neurotoxicity:	0.032	Ototoxicity:	0.917
Hematotoxicity:	0.222	Drug-induced Nephrotoxicity:	0.467
Genotoxicity:	0.883	RPMI-8226 Immunitoxicity:	0.093
A549 Cytotoxicity:	0.365	Hek293 Cytotoxicity:	0.463
BCF:	0.358 ? 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:	2.954 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.292 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.593 ? 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
NPO17292	Asparagus racemosus	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17292	Asparagus racemosus	Species	Asparagaceae	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

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

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 NPC506272 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	20667
0.1-0.2	24970
0.2-0.3	3028
0.3-0.4	945
0.4-0.5	204
0.5-0.6	32
0.6-0.7	10
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
0.7179	Intermediate Similarity	NPC205076
0.6923	Remote Similarity	NPC105511
0.6709	Remote Similarity	NPC197896
0.6709	Remote Similarity	NPC313163
0.6709	Remote Similarity	NPC161749
0.6543	Remote Similarity	NPC100720
0.6098	Remote Similarity	NPC258035
0.6098	Remote Similarity	NPC156457
0.6098	Remote Similarity	NPC603782
0.6047	Remote Similarity	NPC48773
0.6024	Remote Similarity	NPC73511
0.5882	Remote Similarity	NPC481043
0.5854	Remote Similarity	NPC45165
0.5783	Remote Similarity	NPC259070
0.5747	Remote Similarity	NPC307518
0.5714	Remote Similarity	NPC479405
0.5698	Remote Similarity	NPC224462
0.5663	Remote Similarity	NPC135345
0.5652	Remote Similarity	NPC479404
0.5632	Remote Similarity	NPC229729
0.5595	Remote Similarity	NPC211014
0.5595	Remote Similarity	NPC348541
0.5529	Remote Similarity	NPC93337
0.5529	Remote Similarity	NPC146792
0.5517	Remote Similarity	NPC80140
0.5506	Remote Similarity	NPC479407
0.5465	Remote Similarity	NPC105025
0.5402	Remote Similarity	NPC138540
0.5393	Remote Similarity	NPC479406
0.5341	Remote Similarity	NPC479401
0.5287	Remote Similarity	NPC84265
0.5233	Remote Similarity	NPC83283
0.5222	Remote Similarity	NPC607201
0.5172	Remote Similarity	NPC234739
0.5172	Remote Similarity	NPC259152
0.5114	Remote Similarity	NPC24043
0.5114	Remote Similarity	NPC488080
0.5114	Remote Similarity	NPC169977
0.5114	Remote Similarity	NPC610763
0.5057	Remote Similarity	NPC58053
0.5057	Remote Similarity	NPC39360
0.5057	Remote Similarity	NPC29763
0.5057	Remote Similarity	NPC210003

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC506272 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5056
0.1-0.2	4008
0.2-0.3	72
0.3-0.4	9
0.4-0.5	3
0.5-0.6	1
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	Drug ID	Developmental Stage
0.6709	Remote Similarity	NPD4381	Clinical (unspecified phase)
0.5663	Remote Similarity	NPD3818	Discontinued

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