NPASS Compound

Natural Product: NPC515004

Natural Product ID	NPC515004
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Isorhynchospermin
IUPAC Name	3,5-dihydroxy-2-(3-hydroxy-4-methoxy-phenyl)-7-methoxy-6-(3-methylbut-2-enyl)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 51 53 0 0 0 0 0 0 0 0999 V2000 8.3544 -2.0930 0.2175 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1912 -2.4425 -0.5420 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9747 -1.9023 -0.1515 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8523 -1.0570 0.9228 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5982 -0.5329 1.2827 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4493 -0.8222 0.6056 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1209 -0.3139 0.9268 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7961 0.5303 1.9458 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7642 0.9898 2.7941 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4865 0.9747 2.1896 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2508 1.7568 3.1501 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5172 0.5367 1.3597 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8292 0.9337 1.5416 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1640 1.7928 2.5774 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8078 0.4848 0.7044 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2318 0.8563 0.8104 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5203 2.2056 0.3282 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3560 2.4197 -0.6642 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0855 1.3462 -1.3920 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6312 3.8339 -1.1434 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4420 -0.3782 -0.3277 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4174 -0.8415 -1.1788 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0911 -1.7042 -2.2339 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1468 -0.7621 -0.4974 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1271 -0.3169 0.3452 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0895 -0.6975 0.1608 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5951 -1.6886 -0.4900 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8199 -2.1980 -0.8382 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9416 -3.0620 -1.9370 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2342 -2.4565 1.2577 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4457 -0.9759 0.2879 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2577 -2.5500 -0.2282 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7398 -0.7951 1.4952 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5725 0.1200 2.1309 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6957 0.8658 3.8100 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8097 1.5637 3.3024 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5211 0.7110 1.8773 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8269 0.1183 0.2434 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0358 3.0508 0.7989 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5425 0.5878 -0.7134 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4158 0.7909 -2.0915 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9444 1.7589 -1.9623 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1416 4.4195 -0.3591 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6038 4.2593 -1.3165 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2222 3.8515 -2.0623 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9363 -1.8202 -2.9605 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2346 -1.2935 -2.7934 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8729 -2.7421 -1.8851 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8805 -1.4243 -1.2921 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6992 -1.9435 -1.0566 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4256 -3.9450 -1.7364 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 8 10 1 0 10 11 2 0 10 12 1 0 12 13 2 0 13 14 1 0 13 15 1 0 15 16 1 0 16 17 1 0 17 18 2 3 18 19 1 0 18 20 1 0 15 21 2 0 21 22 1 0 22 23 1 0 21 24 1 0 24 25 2 0 25 26 1 0 6 27 1 0 27 28 2 0 28 29 1 0 28 3 1 0 26 7 1 0 25 12 1 0 1 30 1 0 1 31 1 0 1 32 1 0 4 33 1 0 5 34 1 0 9 35 1 0 14 36 1 0 16 37 1 0 16 38 1 0 17 39 1 0 19 40 1 0 19 41 1 0 19 42 1 0 20 43 1 0 20 44 1 0 20 45 1 0 23 46 1 0 23 47 1 0 23 48 1 0 24 49 1 0 27 50 1 0 29 51 1 0 M END

Standard InCHIKey	VADQDPHFUHJWBE-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C22H22O7/c1-11(2)5-7-13-16(28-4)10-17-18(19(13)24)20(25)21(26)22(29-17)12-6-8-15(27-3)14(23)9-12/h5-6,8-10,23-24,26H,7H2,1-4H3
SMILES	COC1=CC=C(C2=C(O)C(=O)C3=C(O)C(CC=C(C)C)=C(OC)C=C3O2)C=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	398.14	Volume:	401.202 ? Van der Waals volume.
Dense:	0.992	LogP:	4.08 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.005 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.949 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	19.0
TPSA:	109.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.555	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.769	Fsp³:	0.227
MCE-18:	21.0 ? 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:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.777	Fluc inhibitor:	0.665 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.944 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.818 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.231	Promiscuous compounds:	0.157

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.205	MDCK Permeability:	-4.768
Pgp-inhibitor:	0.982	Pgp-substrate:	0.018
PAMPA:	0.119 ? 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):	0.672
20% Bioavailability (F20%):	0.513	30% Bioavailability (F30%):	0.975
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.841
Plasma Protein Binding (PPB):	96.733%	Volume Distribution (VD):	-0.103
Fu:	2.688% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.996
BSEP inhibitor:	0.83

ADMET: Metabolism

CYP1A2-inhibitor:	0.693	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.966	CYP2C19-substrate:	0.999
CYP2C9-inhibitor:	0.874	CYP2C9-substrate:	0.013
CYP2D6-inhibitor:	0.852	CYP2D6-substrate:	0.269
CYP3A4-inhibitor:	0.513	CYP3A4-substrate:	0.987
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

4.252

Half-life (T1/2):

1.58

ADMET: Toxicity

hERG Blockers:	0.066	hERG Blockers (10um):	0.477
Human Hepatotoxicity (H-HT):	0.474	Drug-induced Liver Injury (DILI):	0.793
AMES Toxicity:	0.589	Rat Oral Acute Toxicity:	0.707
Maximum Recommended Daily Dose:	0.62	Skin Sensitization:	0.757
Carcinogencity:	0.674	Eye Corrosion:	0.019
Eye Irritation:	0.931	Respiratory Toxicity:	0.855
Drug-induced Neurotoxicity:	0.142	Ototoxicity:	0.234
Hematotoxicity:	0.245	Drug-induced Nephrotoxicity:	0.229
Genotoxicity:	0.727	RPMI-8226 Immunitoxicity:	0.077
A549 Cytotoxicity:	0.316	Hek293 Cytotoxicity:	0.447
BCF:	1.51 ? 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:	4.315 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.49 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.094 ? 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
NPO42626	Paracalyx scariosa	Genus	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 NPC515004 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	20933
0.1-0.2	23935
0.2-0.3	4093
0.3-0.4	718
0.4-0.5	155
0.5-0.6	19
0.6-0.7	2
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
0.6308	Remote Similarity	NPC200740
0.6212	Remote Similarity	NPC93376
0.5821	Remote Similarity	NPC54394
0.5735	Remote Similarity	NPC189179
0.5735	Remote Similarity	NPC75215
0.5694	Remote Similarity	NPC130955
0.5571	Remote Similarity	NPC157784
0.5556	Remote Similarity	NPC14353
0.5556	Remote Similarity	NPC56085
0.5441	Remote Similarity	NPC174999
0.5417	Remote Similarity	NPC165977
0.5362	Remote Similarity	NPC55205
0.5342	Remote Similarity	NPC273538
0.5333	Remote Similarity	NPC488750
0.527	Remote Similarity	NPC604618
0.5211	Remote Similarity	NPC482982
0.5211	Remote Similarity	NPC114377
0.52	Remote Similarity	NPC219917
0.5139	Remote Similarity	NPC24821
0.5072	Remote Similarity	NPC87125
0.5067	Remote Similarity	NPC482708

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC515004 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3291
0.1-0.2	5725
0.2-0.3	128
0.3-0.4	5
0.4-0.5	0
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
0.5342	Remote Similarity	NPD4378	Phase 3

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