NPASS Compound

Natural Product: NPC541667

Natural Product ID	NPC541667
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-hydroxy-7-methoxy-2-[4-methoxy-3-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-phenyl]chroman-4-one
IUPAC Name	(2~{R})-5-hydroxy-7-methoxy-2-[4-methoxy-3-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-phenyl]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 60 63 0 0 0 0 0 0 0 0999 V2000 7.6325 3.2010 2.0005 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3064 2.9902 1.5616 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9668 1.6722 1.1987 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8715 0.6339 1.2638 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5584 -0.6610 0.9132 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4649 -1.7047 0.9778 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2828 -0.9474 0.4744 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8688 -2.2860 0.0840 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6878 -3.2290 0.2454 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5139 -2.4997 -0.4848 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5649 -1.5267 0.1231 C 0 0 2 0 0 0 0 0 0 0 0 0 1.1718 -1.6771 -0.2969 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7992 -2.7443 -1.0776 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5212 -2.9037 -1.4848 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4730 -1.9456 -1.0796 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7614 -2.1309 -1.4963 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2218 -3.1818 -2.2867 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1240 -0.8782 -0.3044 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9898 0.0648 0.1106 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3245 0.2984 -0.0446 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4540 1.4943 -0.7740 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8325 1.6389 -0.9954 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.1089 2.5036 -2.2015 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4905 2.5895 -2.3417 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3751 2.2580 0.2703 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.7233 2.5814 0.1336 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1323 1.3324 1.4071 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.0108 2.1369 2.5672 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9971 0.4049 1.3046 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.4318 -0.9008 1.6237 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2380 -0.7593 0.0861 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0549 -0.2170 -0.0482 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3418 0.0584 0.3920 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6985 1.3638 0.7576 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3633 2.8246 1.2534 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7798 4.2766 2.1792 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8367 2.6818 2.9655 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8739 0.8387 1.6045 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8088 -2.0059 1.8876 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2482 -3.5625 -0.2762 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5509 -2.2981 -1.5853 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5797 -1.7127 1.2356 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5616 -3.4491 -1.3637 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8324 -3.7375 -2.0992 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9391 -4.1796 -1.9070 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3475 -3.1400 -2.2629 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9318 -3.0045 -3.3317 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8608 -0.4487 -0.6535 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2673 0.6392 -1.1205 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7143 3.5220 -2.0183 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6960 2.0187 -3.0830 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7344 3.4044 -2.8846 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7650 3.1872 0.4442 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9133 3.2799 0.8112 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0988 0.7713 1.5806 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0741 1.5189 3.3448 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2242 0.6509 2.0716 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7038 -1.3580 0.7659 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4806 0.0951 0.6982 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9682 2.1584 0.6965 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 5 7 2 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 15 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 22 25 1 0 25 26 1 0 25 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 18 31 2 0 11 32 1 0 32 33 1 0 33 34 2 0 34 3 1 0 33 7 1 0 31 12 1 0 29 20 1 0 1 35 1 0 1 36 1 0 1 37 1 0 4 38 1 0 6 39 1 0 10 40 1 0 10 41 1 0 11 42 1 1 13 43 1 0 14 44 1 0 17 45 1 0 17 46 1 0 17 47 1 0 20 48 1 6 22 49 1 6 23 50 1 0 23 51 1 0 24 52 1 0 25 53 1 1 26 54 1 0 27 55 1 1 28 56 1 0 29 57 1 1 30 58 1 0 31 59 1 0 34 60 1 0 M END

Standard InCHIKey	VHGJMSVFUPCQGC-BHTFSWEFSA-N
Standard InCHI	InChI=1S/C23H26O11/c1-30-11-6-12(25)19-13(26)8-15(32-17(19)7-11)10-3-4-14(31-2)16(5-10)33-23-22(29)21(28)20(27)18(9-24)34-23/h3-7,15,18,20-25,27-29H,8-9H2,1-2H3/t15-,18-,20-,21+,22-,23-/m1/s1
SMILES	COC1=CC(O)=C2C(=O)C[C@H](C3=CC=C(OC)C(O[C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)=C3)OC2=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	478.15	Volume:	450.376 ? Van der Waals volume.
Dense:	1.062	LogP:	1.2 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.689 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.156 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	24.0
TPSA:	164.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.388	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.999	Fsp³:	0.435
MCE-18:	89.03 ? 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:	0.588	Fluc inhibitor:	0.309 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.144 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.507 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.089	Promiscuous compounds:	0.383

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.22	MDCK Permeability:	-5.164
Pgp-inhibitor:	0.564	Pgp-substrate:	0.05
PAMPA:	0.721 ? 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):	0.488
20% Bioavailability (F20%):	0.0	30% Bioavailability (F30%):	0.985
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.04
Plasma Protein Binding (PPB):	92.938%	Volume Distribution (VD):	-0.142
Fu:	6.882% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.998
BSEP inhibitor:	0.401

ADMET: Metabolism

CYP1A2-inhibitor:	0.559	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.007
CYP2C9-inhibitor:	0.019	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.609
HLM stability:	0.564 ? 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):

2.85

Half-life (T1/2):

3.552

ADMET: Toxicity

hERG Blockers:	0.04	hERG Blockers (10um):	0.123
Human Hepatotoxicity (H-HT):	0.8	Drug-induced Liver Injury (DILI):	0.968
AMES Toxicity:	0.954	Rat Oral Acute Toxicity:	0.051
Maximum Recommended Daily Dose:	0.077	Skin Sensitization:	0.972
Carcinogencity:	0.558	Eye Corrosion:	0.0
Eye Irritation:	0.27	Respiratory Toxicity:	0.026
Drug-induced Neurotoxicity:	0.062	Ototoxicity:	0.928
Hematotoxicity:	0.481	Drug-induced Nephrotoxicity:	0.913
Genotoxicity:	0.886	RPMI-8226 Immunitoxicity:	0.208
A549 Cytotoxicity:	0.443	Hek293 Cytotoxicity:	0.407
BCF:	0.647 ? 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:	3.297 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.13 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.147 ? 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
NPO30692	Prunus amygdalus	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30692	Prunus amygdalus	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30692	Prunus amygdalus	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

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 NPC541667 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	16046
0.1-0.2	28145
0.2-0.3	4587
0.3-0.4	813
0.4-0.5	205
0.5-0.6	49
0.6-0.7	4
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
0.8143	Intermediate Similarity	NPC219163
0.7838	Intermediate Similarity	NPC236934
0.75	Intermediate Similarity	NPC97052
0.7397	Intermediate Similarity	NPC39351
0.72	Intermediate Similarity	NPC29830
0.6711	Remote Similarity	NPC26195
0.6706	Remote Similarity	NPC293629
0.6203	Remote Similarity	NPC206378
0.6173	Remote Similarity	NPC472383
0.5977	Remote Similarity	NPC97285
0.5949	Remote Similarity	NPC170475
0.5915	Remote Similarity	NPC23084
0.5854	Remote Similarity	NPC5778
0.5802	Remote Similarity	NPC106625
0.5778	Remote Similarity	NPC105095
0.5778	Remote Similarity	NPC177731
0.5778	Remote Similarity	NPC725
0.5765	Remote Similarity	NPC472382
0.5747	Remote Similarity	NPC105283
0.5667	Remote Similarity	NPC44328
0.5667	Remote Similarity	NPC79056
0.5663	Remote Similarity	NPC300537
0.5625	Remote Similarity	NPC169248
0.5625	Remote Similarity	NPC72649
0.5595	Remote Similarity	NPC472381
0.5556	Remote Similarity	NPC163191
0.5507	Remote Similarity	NPC6407
0.5507	Remote Similarity	NPC545184
0.5488	Remote Similarity	NPC471457
0.5444	Remote Similarity	NPC142860
0.5444	Remote Similarity	NPC152538
0.5444	Remote Similarity	NPC246469
0.5444	Remote Similarity	NPC89088
0.5375	Remote Similarity	NPC99233
0.5357	Remote Similarity	NPC181014
0.5333	Remote Similarity	NPC271270
0.5326	Remote Similarity	NPC291124
0.5326	Remote Similarity	NPC131157
0.5316	Remote Similarity	NPC604892
0.5263	Remote Similarity	NPC261254
0.5233	Remote Similarity	NPC477502
0.5217	Remote Similarity	NPC43587
0.5211	Remote Similarity	NPC150648
0.5205	Remote Similarity	NPC18727
0.519	Remote Similarity	NPC246947
0.5152	Remote Similarity	NPC241196
0.5152	Remote Similarity	NPC318119
0.5139	Remote Similarity	NPC329203
0.5139	Remote Similarity	NPC222342
0.5132	Remote Similarity	NPC479029
0.5128	Remote Similarity	NPC477840
0.5122	Remote Similarity	NPC606849
0.5104	Remote Similarity	NPC67134
0.5063	Remote Similarity	NPC276753
0.5063	Remote Similarity	NPC205796
0.5059	Remote Similarity	NPC227902
0.505	Remote Similarity	NPC321916
0.5049	Remote Similarity	NPC488528

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC541667 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4348
0.1-0.2	4656
0.2-0.3	127
0.3-0.4	16
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
0.5667	Remote Similarity	NPD7074	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