NPASS Compound

Natural Product: NPC575058

Natural Product ID	NPC575058
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{R})-8-[(2~{R})-2,3-dihydroxy-3-methyl-butyl]-7-hydroxy-2-(4-hydroxyphenyl)chroman-4-one
IUPAC Name	(2~{R})-8-[(2~{R})-2,3-dihydroxy-3-methyl-butyl]-7-hydroxy-2-(4-hydroxyphenyl)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 48 50 0 0 0 0 0 0 0 0999 V2000 2.8124 -0.1121 2.5567 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5920 -0.6138 1.3727 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0729 -0.3383 1.6576 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4447 -1.9676 1.2300 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2288 0.1598 0.0945 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4414 1.5004 0.4509 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8307 -0.1649 -0.2241 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2180 0.4293 -1.3971 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8826 1.1916 -2.3270 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2350 1.4096 -2.1411 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1952 1.7189 -3.4172 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1653 1.4623 -3.5472 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8481 0.6996 -2.6243 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1588 0.1825 -1.5490 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8764 -0.5708 -0.6541 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2004 -1.0021 -0.7856 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0773 -0.5053 0.2989 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0589 0.7934 0.7480 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8909 1.2203 1.7594 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7754 0.3360 2.3523 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6217 0.7387 3.3697 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7958 -0.9501 1.9098 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9615 -1.3683 0.8992 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8409 -0.7199 -2.1045 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2795 0.4602 -2.8106 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9916 1.1921 -3.5139 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9950 0.9763 2.7434 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7545 -0.3876 2.5520 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2611 -0.6263 3.4526 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7185 -0.8790 0.9242 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2404 0.7502 1.5021 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3216 -0.5597 2.6981 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0277 -2.3256 2.0446 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9566 -0.2137 -0.6509 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5404 1.8508 0.7165 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7269 -1.2756 -0.2423 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2006 0.1454 0.6634 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8570 1.3168 -2.9469 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7652 2.3102 -4.1171 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7016 1.8717 -4.3949 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1555 -2.1292 -0.6979 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3895 1.4885 0.3082 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8938 2.2424 2.1306 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4740 0.2223 3.5653 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4621 -1.6972 2.3272 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9975 -2.4034 0.5628 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9221 -0.5272 -1.9494 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7808 -1.5991 -2.7955 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 2 5 1 0 5 6 1 0 5 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 20 22 1 0 22 23 2 0 16 24 1 0 24 25 1 0 25 26 2 0 14 8 1 0 23 17 1 0 25 13 1 0 1 27 1 0 1 28 1 0 1 29 1 0 3 30 1 0 3 31 1 0 3 32 1 0 4 33 1 0 5 34 1 6 6 35 1 0 7 36 1 0 7 37 1 0 10 38 1 0 11 39 1 0 12 40 1 0 16 41 1 1 18 42 1 0 19 43 1 0 21 44 1 0 22 45 1 0 23 46 1 0 24 47 1 0 24 48 1 0 M END

Standard InCHIKey	MCDSHLATEYMKDN-QZTJIDSGSA-N
Standard InCHI	InChI=1S/C20H22O6/c1-20(2,25)18(24)9-14-15(22)8-7-13-16(23)10-17(26-19(13)14)11-3-5-12(21)6-4-11/h3-8,17-18,21-22,24-25H,9-10H2,1-2H3/t17-,18-/m1/s1
SMILES	CC(C)(O)[C@H](O)CC1=C(O)C=CC2=C1O[C@@H](C1=CC=C(O)C=C1)CC2=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	358.14	Volume:	363.093 ? Van der Waals volume.
Dense:	0.986	LogP:	2.158 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.247 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.349 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	18.0
TPSA:	107.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.669	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.468	Fsp³:	0.35
MCE-18:	66.111 ? 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:	0.615	Fluc inhibitor:	0.513 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.276 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.121 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.159	Promiscuous compounds:	0.196

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.224	MDCK Permeability:	-4.742
Pgp-inhibitor:	0.088	Pgp-substrate:	0.368
PAMPA:	0.745 ? 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):	0.0
20% Bioavailability (F20%):	0.001	30% Bioavailability (F30%):	0.521
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.797
Plasma Protein Binding (PPB):	89.085%	Volume Distribution (VD):	-0.028
Fu:	13.159% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.852
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.999
BSEP inhibitor:	0.653

ADMET: Metabolism

CYP1A2-inhibitor:	0.047	CYP1A2-substrate:	0.204
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.406
CYP2C9-inhibitor:	0.016	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.695	CYP2D6-substrate:	0.877
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.806
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.925
HLM stability:	0.748 ? 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):

4.833

Half-life (T1/2):

1.789

ADMET: Toxicity

hERG Blockers:	0.156	hERG Blockers (10um):	0.448
Human Hepatotoxicity (H-HT):	0.674	Drug-induced Liver Injury (DILI):	0.049
AMES Toxicity:	0.663	Rat Oral Acute Toxicity:	0.45
Maximum Recommended Daily Dose:	0.699	Skin Sensitization:	0.749
Carcinogencity:	0.501	Eye Corrosion:	0.001
Eye Irritation:	0.94	Respiratory Toxicity:	0.12
Drug-induced Neurotoxicity:	0.829	Ototoxicity:	0.474
Hematotoxicity:	0.079	Drug-induced Nephrotoxicity:	0.629
Genotoxicity:	0.893	RPMI-8226 Immunitoxicity:	0.084
A549 Cytotoxicity:	0.284	Hek293 Cytotoxicity:	0.58
BCF:	0.616 ? 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:	3.313 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.597 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.009 ? 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
NPO14009	Brosimum acutifolium	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14009	Brosimum acutifolium	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14009	Brosimum acutifolium	Species	Moraceae	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 NPC575058 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	16036
0.1-0.2	28587
0.2-0.3	4569
0.3-0.4	530
0.4-0.5	106
0.5-0.6	22
0.6-0.7	4
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
0.7069	Intermediate Similarity	NPC164980
0.7031	Intermediate Similarity	NPC479214
0.6515	Remote Similarity	NPC479211
0.6418	Remote Similarity	NPC479213
0.6232	Remote Similarity	NPC479217
0.6212	Remote Similarity	NPC36275
0.5873	Remote Similarity	NPC150408
0.5857	Remote Similarity	NPC479215
0.5781	Remote Similarity	NPC149026
0.5775	Remote Similarity	NPC479212
0.5714	Remote Similarity	NPC480991
0.5634	Remote Similarity	NPC477958
0.5625	Remote Similarity	NPC91560
0.5625	Remote Similarity	NPC236766
0.5538	Remote Similarity	NPC75049
0.5493	Remote Similarity	NPC477957
0.5439	Remote Similarity	NPC329225
0.5439	Remote Similarity	NPC147686
0.5417	Remote Similarity	NPC479221
0.5205	Remote Similarity	NPC479207
0.5167	Remote Similarity	NPC603284
0.5152	Remote Similarity	NPC107572
0.5152	Remote Similarity	NPC472580
0.5152	Remote Similarity	NPC32739
0.5135	Remote Similarity	NPC479218
0.5082	Remote Similarity	NPC167624
0.5082	Remote Similarity	NPC166482
0.507	Remote Similarity	NPC473015

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC575058 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3087
0.1-0.2	5852
0.2-0.3	201
0.3-0.4	7
0.4-0.5	2
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
0.5439	Remote Similarity	NPD1549	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