NPASS Compound

Natural Product: NPC512005

Natural Product ID	NPC512005
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{R})-5,7-dihydroxy-2-(4-methoxyphenyl)-8-methyl-chroman-4-one
IUPAC Name	(2~{R})-5,7-dihydroxy-2-(4-methoxyphenyl)-8-methyl-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 38 40 0 0 0 0 0 0 0 0999 V2000 6.4568 -0.1420 -0.0497 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2992 -0.4365 -0.8084 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0330 -0.0952 -0.3468 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9480 -0.4217 -1.1562 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6605 -0.1179 -0.7708 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4543 0.5131 0.4246 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0617 0.8435 0.8449 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4419 2.0544 0.0808 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9164 2.1496 0.1461 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5325 3.2370 0.3013 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6930 0.9245 0.0246 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0375 0.9136 -0.3097 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6599 2.1343 -0.5366 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7003 -0.2973 -0.4036 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0397 -1.5000 -0.1683 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7274 -2.7046 -0.2688 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7075 -1.5000 0.1636 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9618 -2.7624 0.4237 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0614 -0.2663 0.2520 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7226 -0.3018 0.5877 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5271 0.8363 1.2257 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8207 0.5362 0.8486 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7775 0.9153 -0.1783 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2781 -0.8367 -0.3627 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2779 -0.3487 1.0350 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1104 -0.9174 -2.0952 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8419 -0.3903 -1.4322 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0109 1.0857 1.9224 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1306 1.8776 -0.9902 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0541 2.9552 0.4907 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6846 2.1890 -0.5993 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7460 -0.3081 -0.6635 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6426 -2.8022 -0.6384 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0425 -3.4432 -0.4304 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2924 -3.1979 1.3866 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8844 -2.5081 0.5570 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3635 1.3359 2.1721 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6493 0.7970 1.4890 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 1 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 12 14 1 0 14 15 2 0 15 16 1 0 15 17 1 0 17 18 1 0 17 19 2 0 19 20 1 0 6 21 1 0 21 22 2 0 22 3 1 0 20 7 1 0 19 11 1 0 1 23 1 0 1 24 1 0 1 25 1 0 4 26 1 0 5 27 1 0 7 28 1 1 8 29 1 0 8 30 1 0 13 31 1 0 14 32 1 0 16 33 1 0 18 34 1 0 18 35 1 0 18 36 1 0 21 37 1 0 22 38 1 0 M END

Standard InCHIKey	ZUPNDQXBQBIBPZ-OAHLLOKOSA-N
Standard InCHI	InChI=1S/C17H16O5/c1-9-12(18)7-13(19)16-14(20)8-15(22-17(9)16)10-3-5-11(21-2)6-4-10/h3-7,15,18-19H,8H2,1-2H3/t15-/m1/s1
SMILES	COC1=CC=C([C@H]2CC(=O)C3=C(O)C=C(O)C(C)=C3O2)C=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	300.1	Volume:	302.415 ? Van der Waals volume.
Dense:	0.992	LogP:	3.36 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.139 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.876 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
TPSA:	75.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.891	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.87	Fsp³:	0.235
MCE-18:	57.429 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.633	Fluc inhibitor:	0.954 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.39 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.307 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.317	Promiscuous compounds:	0.092

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.036	MDCK Permeability:	-4.777
Pgp-inhibitor:	0.995	Pgp-substrate:	0.083
PAMPA:	0.106 ? 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):	0.004
20% Bioavailability (F20%):	0.004	30% Bioavailability (F30%):	0.734
50% Bioavailability (F50%):	0.975

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.921
Plasma Protein Binding (PPB):	97.806%	Volume Distribution (VD):	0.169
Fu:	1.886% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.99
BSEP inhibitor:	0.965

ADMET: Metabolism

CYP1A2-inhibitor:	0.999	CYP1A2-substrate:	0.968
CYP2C19-inhibitor:	0.721	CYP2C19-substrate:	0.997
CYP2C9-inhibitor:	0.839	CYP2C9-substrate:	0.096
CYP2D6-inhibitor:	0.953	CYP2D6-substrate:	0.985
CYP3A4-inhibitor:	0.277	CYP3A4-substrate:	0.987
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.998
HLM stability:	0.996 ? 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):

3.261

Half-life (T1/2):

1.292

ADMET: Toxicity

hERG Blockers:	0.084	hERG Blockers (10um):	0.462
Human Hepatotoxicity (H-HT):	0.699	Drug-induced Liver Injury (DILI):	0.413
AMES Toxicity:	0.781	Rat Oral Acute Toxicity:	0.525
Maximum Recommended Daily Dose:	0.522	Skin Sensitization:	0.674
Carcinogencity:	0.632	Eye Corrosion:	0.028
Eye Irritation:	0.992	Respiratory Toxicity:	0.696
Drug-induced Neurotoxicity:	0.512	Ototoxicity:	0.353
Hematotoxicity:	0.285	Drug-induced Nephrotoxicity:	0.603
Genotoxicity:	0.874	RPMI-8226 Immunitoxicity:	0.181
A549 Cytotoxicity:	0.396	Hek293 Cytotoxicity:	0.568
BCF:	1.529 ? 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:	4.137 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.75 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.884 ? 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
NPO4363	Amaranthus caudatus	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4363	Amaranthus caudatus	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4363	Amaranthus caudatus	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4363	Amaranthus caudatus	Species	Amaranthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4363	Amaranthus caudatus	Species	Amaranthaceae	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 NPC512005 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	25674
0.1-0.2	19869
0.2-0.3	3633
0.3-0.4	492
0.4-0.5	129
0.5-0.6	43
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
0.7826	Intermediate Similarity	NPC213322
0.766	Intermediate Similarity	NPC603284
0.7347	Intermediate Similarity	NPC296917
0.7347	Intermediate Similarity	NPC170907
0.6909	Remote Similarity	NPC148757
0.68	Remote Similarity	NPC20354
0.6667	Remote Similarity	NPC274784
0.6667	Remote Similarity	NPC20709
0.6471	Remote Similarity	NPC4743
0.6275	Remote Similarity	NPC482121
0.6275	Remote Similarity	NPC6407
0.6275	Remote Similarity	NPC270964
0.6275	Remote Similarity	NPC545184
0.6038	Remote Similarity	NPC194432
0.5849	Remote Similarity	NPC162869
0.5818	Remote Similarity	NPC469758
0.5769	Remote Similarity	NPC188243
0.5769	Remote Similarity	NPC110228
0.5741	Remote Similarity	NPC110038
0.566	Remote Similarity	NPC248372
0.5636	Remote Similarity	NPC485881
0.5636	Remote Similarity	NPC480995
0.5636	Remote Similarity	NPC477503
0.5556	Remote Similarity	NPC167624
0.5556	Remote Similarity	NPC166482
0.5556	Remote Similarity	NPC177354
0.5536	Remote Similarity	NPC2416
0.5484	Remote Similarity	NPC291878
0.5455	Remote Similarity	NPC215885
0.5455	Remote Similarity	NPC110776
0.5424	Remote Similarity	NPC76372
0.5424	Remote Similarity	NPC37496
0.5424	Remote Similarity	NPC480991
0.541	Remote Similarity	NPC480990
0.5397	Remote Similarity	NPC161506
0.5357	Remote Similarity	NPC480992
0.5352	Remote Similarity	NPC475184
0.5333	Remote Similarity	NPC109183
0.5333	Remote Similarity	NPC107572
0.5333	Remote Similarity	NPC32739
0.5273	Remote Similarity	NPC150648
0.5254	Remote Similarity	NPC270789
0.5246	Remote Similarity	NPC149026
0.5179	Remote Similarity	NPC480993
0.5179	Remote Similarity	NPC329203
0.5179	Remote Similarity	NPC156057
0.5179	Remote Similarity	NPC222342
0.5172	Remote Similarity	NPC302950
0.5161	Remote Similarity	NPC470133
0.5091	Remote Similarity	NPC32441
0.5091	Remote Similarity	NPC243083
0.5091	Remote Similarity	NPC13768
0.5091	Remote Similarity	NPC287246
0.5091	Remote Similarity	NPC79943
0.5088	Remote Similarity	NPC476153
0.5088	Remote Similarity	NPC192083
0.5085	Remote Similarity	NPC231134

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC512005 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4252
0.1-0.2	4730
0.2-0.3	155
0.3-0.4	8
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
0.5172	Remote Similarity	NPD1934	Phase 0
0.5091	Remote Similarity	NPD1550	Phase 2
0.5091	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.5088	Remote Similarity	NPD2393	Clinical (unspecified phase)

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