NPASS Compound

Natural Product: NPC494036

Natural Product ID	NPC494036
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{S})-5,7-dihydroxy-2-[4-[(2~{S},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxyphenyl]chroman-4-one
IUPAC Name	(2~{S})-5,7-dihydroxy-2-[4-[(2~{S},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxyphenyl]chroman-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 52 55 0 0 0 0 0 0 0 0999 V2000 6.3631 -0.0960 -2.2705 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6766 -0.1199 -0.9051 C 0 0 2 0 0 0 0 0 0 0 0 0 4.3403 -0.3065 -1.1289 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5210 -0.0686 -0.0206 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6251 -1.1134 0.0726 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2590 -0.9936 -0.0244 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5821 0.1804 -0.2275 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8126 0.2199 -0.3151 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5856 -0.9099 -0.2034 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0460 -0.9298 -0.2867 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.5852 -0.7359 -1.6783 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0854 -0.8096 -1.5622 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7962 -1.3903 -2.4070 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7439 -0.1785 -0.4176 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1233 -0.0534 -0.3515 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9224 -0.5290 -1.3814 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7081 0.5471 0.7435 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9308 1.0353 1.7950 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5135 1.6428 2.9037 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5619 0.8929 1.6938 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9514 0.2905 0.5985 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5741 0.1493 0.5012 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8986 -2.0871 0.0007 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4644 -2.1494 0.0896 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3543 0.0884 1.2434 C 0 0 1 0 0 0 0 0 0 0 0 0 4.9456 -1.0744 1.6645 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2819 1.2536 1.0746 C 0 0 2 0 0 0 0 0 0 0 0 0 4.5365 2.4306 1.2322 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8860 1.2625 -0.3146 C 0 0 1 0 0 0 0 0 0 0 0 0 7.2673 1.4747 -0.2797 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3992 0.2815 -2.2053 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3639 -1.1135 -2.7253 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8157 0.5672 -2.9705 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1536 -0.9173 -0.3249 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0316 0.8982 -0.1834 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1431 1.0979 -0.3221 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2964 1.1660 -0.4751 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4966 -1.8563 0.1238 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2074 -1.4611 -2.4059 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3725 0.3200 -1.9652 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1243 -1.5394 -1.3562 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7847 0.6704 0.8450 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5422 2.6576 2.9955 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8933 1.2472 2.4703 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4909 -3.0099 0.0944 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9779 -3.0952 0.2515 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6138 0.3854 2.0428 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9648 -1.1653 2.6578 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0783 1.2723 1.8465 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4266 2.6774 2.1866 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3857 1.9857 -0.9666 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5897 1.0085 0.5475 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 2 0 15 16 1 0 15 17 1 0 17 18 2 0 18 19 1 0 18 20 1 0 20 21 2 0 21 22 1 0 9 23 1 0 23 24 2 0 4 25 1 0 25 26 1 0 25 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 29 2 1 0 24 6 1 0 22 10 1 0 21 14 1 0 1 31 1 0 1 32 1 0 1 33 1 0 2 34 1 1 4 35 1 6 7 36 1 0 8 37 1 0 10 38 1 1 11 39 1 0 11 40 1 0 16 41 1 0 17 42 1 0 19 43 1 0 20 44 1 0 23 45 1 0 24 46 1 0 25 47 1 1 26 48 1 0 27 49 1 1 28 50 1 0 29 51 1 6 30 52 1 0 M END

Standard InCHIKey	SMIANZMWOZURTO-AYEDQIRASA-N
Standard InCHI	InChI=1S/C21H22O9/c1-9-18(25)19(26)20(27)21(28-9)29-12-4-2-10(3-5-12)15-8-14(24)17-13(23)6-11(22)7-16(17)30-15/h2-7,9,15,18-23,25-27H,8H2,1H3/t9-,15-,18-,19+,20-,21-/m0/s1
SMILES	C[C@@H]1O[C@@H](OC2=CC=C([C@@H]3CC(=O)C4=C(O)C=C(O)C=C4O3)C=C2)[C@@H](O)[C@H](O)[C@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	418.13	Volume:	398.203 ? Van der Waals volume.
Dense:	1.05	LogP:	1.824 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.081 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.72 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	24.0
TPSA:	145.91 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.493	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.976	Fsp³:	0.381
MCE-18:	87.069 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.624	Fluc inhibitor:	0.598 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.14 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.495 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.168	Promiscuous compounds:	0.261

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.328	MDCK Permeability:	-5.092
Pgp-inhibitor:	0.023	Pgp-substrate:	0.196
PAMPA:	0.846 ? 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):	0.007
20% Bioavailability (F20%):	0.006	30% Bioavailability (F30%):	0.689
50% Bioavailability (F50%):	0.957

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.145
Plasma Protein Binding (PPB):	93.8%	Volume Distribution (VD):	-0.275
Fu:	4.887% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.985
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.916
BSEP inhibitor:	0.465

ADMET: Metabolism

CYP1A2-inhibitor:	0.302	CYP1A2-substrate:	0.072
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.346
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.219
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.621
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.982
HLM stability:	0.925 ? 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):

3.357

Half-life (T1/2):

3.763

ADMET: Toxicity

hERG Blockers:	0.086	hERG Blockers (10um):	0.406
Human Hepatotoxicity (H-HT):	0.676	Drug-induced Liver Injury (DILI):	0.956
AMES Toxicity:	0.882	Rat Oral Acute Toxicity:	0.342
Maximum Recommended Daily Dose:	0.571	Skin Sensitization:	0.788
Carcinogencity:	0.181	Eye Corrosion:	0.0
Eye Irritation:	0.768	Respiratory Toxicity:	0.571
Drug-induced Neurotoxicity:	0.135	Ototoxicity:	0.898
Hematotoxicity:	0.116	Drug-induced Nephrotoxicity:	0.868
Genotoxicity:	0.986	RPMI-8226 Immunitoxicity:	0.24
A549 Cytotoxicity:	0.67	Hek293 Cytotoxicity:	0.588
BCF:	0.838 ? 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:	3.572 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.905 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.238 ? 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
NPO59643	Crotalaria striata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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 NPC494036 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	14777
0.1-0.2	30370
0.2-0.3	3731
0.3-0.4	776
0.4-0.5	139
0.5-0.6	53
0.6-0.7	7
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8333	Intermediate Similarity	NPC26195
0.6351	Remote Similarity	NPC219163
0.6349	Remote Similarity	NPC274784
0.6349	Remote Similarity	NPC20709
0.6216	Remote Similarity	NPC170475
0.6133	Remote Similarity	NPC39351
0.6098	Remote Similarity	NPC271270
0.6	Remote Similarity	NPC97052
0.5921	Remote Similarity	NPC127782
0.5781	Remote Similarity	NPC32441
0.5781	Remote Similarity	NPC243083
0.5781	Remote Similarity	NPC13768
0.5781	Remote Similarity	NPC287246
0.5781	Remote Similarity	NPC79943
0.5747	Remote Similarity	NPC168789
0.5698	Remote Similarity	NPC44328
0.5698	Remote Similarity	NPC79056
0.5647	Remote Similarity	NPC97285
0.5632	Remote Similarity	NPC293629
0.5616	Remote Similarity	NPC174953
0.5588	Remote Similarity	NPC302950
0.5581	Remote Similarity	NPC43587
0.557	Remote Similarity	NPC29830
0.5556	Remote Similarity	NPC199335
0.5517	Remote Similarity	NPC70441
0.5479	Remote Similarity	NPC190217
0.5465	Remote Similarity	NPC142860
0.5465	Remote Similarity	NPC152538
0.5465	Remote Similarity	NPC246469
0.5465	Remote Similarity	NPC89088
0.5455	Remote Similarity	NPC169248
0.5455	Remote Similarity	NPC72649
0.5385	Remote Similarity	NPC182421
0.5375	Remote Similarity	NPC181014
0.5366	Remote Similarity	NPC236934
0.5342	Remote Similarity	NPC477240
0.5325	Remote Similarity	NPC153342
0.5309	Remote Similarity	NPC5778
0.5294	Remote Similarity	NPC321011
0.5294	Remote Similarity	NPC294852
0.5294	Remote Similarity	NPC188679
0.5263	Remote Similarity	NPC475790
0.5256	Remote Similarity	NPC270578
0.5256	Remote Similarity	NPC52382
0.5211	Remote Similarity	NPC236637
0.5205	Remote Similarity	NPC477841
0.5195	Remote Similarity	NPC482602
0.5147	Remote Similarity	NPC338131
0.5139	Remote Similarity	NPC258630
0.5135	Remote Similarity	NPC109223
0.5135	Remote Similarity	NPC10937
0.5111	Remote Similarity	NPC105095
0.5111	Remote Similarity	NPC177731
0.5111	Remote Similarity	NPC725
0.5075	Remote Similarity	NPC295261
0.5075	Remote Similarity	NPC296490
0.5068	Remote Similarity	NPC106025
0.5067	Remote Similarity	NPC106976
0.5065	Remote Similarity	NPC470890
0.5062	Remote Similarity	NPC206378
0.5059	Remote Similarity	NPC472382

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC494036 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3750
0.1-0.2	5273
0.2-0.3	111
0.3-0.4	11
0.4-0.5	1
0.5-0.6	4
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
0.5781	Remote Similarity	NPD1550	Phase 2
0.5781	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.5698	Remote Similarity	NPD7074	Phase 3
0.5588	Remote Similarity	NPD1934	Phase 0

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