NPASS Compound

Natural Product: NPC586408

Natural Product ID	NPC586408
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5,6-dihydroxy-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one
IUPAC Name	5,6-dihydroxy-7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-2-(3,4,5-trihydroxyphenyl)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 54 57 0 0 0 0 0 0 0 0999 V2000 2.5441 -3.3911 1.8489 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6401 -2.3222 1.2084 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8522 -1.7990 0.7921 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9327 -0.6212 0.0886 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2028 -0.0351 -0.3699 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3734 -0.6591 -0.1043 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5499 -0.0558 -0.5648 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7832 -0.6499 -0.3223 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5421 1.1278 -1.2638 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7218 1.7261 -1.7215 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3606 1.7488 -1.5267 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2858 2.9385 -2.2234 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2012 1.1598 -1.0763 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7897 -0.0188 -0.1669 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6146 -0.4680 0.2024 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4630 0.2146 -0.0997 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8174 -0.2113 0.2650 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8502 0.5513 -0.0948 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1923 0.3978 0.1144 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.8067 0.3429 -1.1558 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1304 -0.0345 -0.9499 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.7778 -0.5409 -2.2240 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0782 -0.8969 -1.9584 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8502 1.1767 -0.3913 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.2122 1.0063 -0.3046 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2457 1.4386 0.9832 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.8359 2.5147 1.6032 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7612 1.5861 0.8958 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2471 1.4628 2.1925 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9128 -1.3779 0.9633 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0964 -1.9443 1.4025 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2387 -2.1145 1.2973 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1853 -3.2908 1.9976 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4732 -1.6433 0.9098 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7476 -2.3461 1.0367 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4914 -1.5818 0.4307 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8732 -1.6557 -0.2945 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4563 1.8947 -1.0185 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4325 3.2858 -2.6266 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2323 1.6078 -1.2556 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5282 1.1369 -0.6508 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5257 -0.4868 0.6665 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1359 -0.8574 -0.1973 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2259 -1.4562 -2.5133 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6784 0.2066 -3.0314 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1155 -1.3310 -1.0646 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5703 2.0352 -1.0610 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5917 1.2886 -1.1956 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4444 0.4984 1.5730 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7544 2.4494 2.5899 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4244 2.5457 0.4842 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7893 2.2784 2.4909 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5539 -2.6716 0.8820 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1080 -4.1590 1.4843 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 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 7 9 2 0 9 10 1 0 9 11 1 0 11 12 1 0 11 13 2 0 4 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 21 24 1 0 24 25 1 0 24 26 1 0 26 27 1 0 26 28 1 0 28 29 1 0 17 30 2 0 30 31 1 0 30 32 1 0 32 33 1 0 32 34 2 0 34 2 1 0 13 5 1 0 34 15 1 0 28 19 1 0 3 35 1 0 6 36 1 0 8 37 1 0 10 38 1 0 12 39 1 0 13 40 1 0 16 41 1 0 19 42 1 1 21 43 1 1 22 44 1 0 22 45 1 0 23 46 1 0 24 47 1 6 25 48 1 0 26 49 1 1 27 50 1 0 28 51 1 6 29 52 1 0 31 53 1 0 33 54 1 0 M END

Standard InCHIKey	QGBOMGIZGLUTDW-JNHRPPPUSA-N
Standard InCHI	InChI=1S/C21H20O13/c22-5-13-17(28)19(30)20(31)21(34-13)33-12-4-11-14(18(29)16(12)27)7(23)3-10(32-11)6-1-8(24)15(26)9(25)2-6/h1-4,13,17,19-22,24-31H,5H2/t13-,17-,19+,20-,21-/m1/s1
SMILES	O=C1C=C(C2=CC(O)=C(O)C(O)=C2)OC2=CC(O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)=C(O)C(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	480.09	Volume:	430.728 ? Van der Waals volume.
Dense:	1.115	LogP:	0.238 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.876 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.306 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	24.0
TPSA:	230.74 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	9.0	Rings:	4.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.208	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.187	Fsp³:	0.286
MCE-18:	94.37 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.768	Fluc inhibitor:	0.207 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.965 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.779 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.359	Promiscuous compounds:	0.922

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.402	MDCK Permeability:	-4.924
Pgp-inhibitor:	0.0	Pgp-substrate:	0.062
PAMPA:	0.999 ? 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):	0.851
20% Bioavailability (F20%):	0.926	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.815
Plasma Protein Binding (PPB):	78.472%	Volume Distribution (VD):	-0.003
Fu:	18.753% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.973
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.004
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.989
HLM stability:	0.0 ? 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):

3.687

Half-life (T1/2):

4.362

ADMET: Toxicity

hERG Blockers:	0.013	hERG Blockers (10um):	0.261
Human Hepatotoxicity (H-HT):	0.53	Drug-induced Liver Injury (DILI):	0.972
AMES Toxicity:	0.909	Rat Oral Acute Toxicity:	0.034
Maximum Recommended Daily Dose:	0.142	Skin Sensitization:	1.0
Carcinogencity:	0.17	Eye Corrosion:	0.0
Eye Irritation:	0.707	Respiratory Toxicity:	0.015
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.981
Hematotoxicity:	0.043	Drug-induced Nephrotoxicity:	0.047
Genotoxicity:	0.992	RPMI-8226 Immunitoxicity:	0.011
A549 Cytotoxicity:	0.961	Hek293 Cytotoxicity:	0.234
BCF:	0.318 ? 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:	2.806 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.247 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.49 ? 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
NPO63799	Halophila ovalis	Species	Hydrocharitaceae	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 NPC586408 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	24543
0.1-0.2	21786
0.2-0.3	2410
0.3-0.4	785
0.4-0.5	249
0.5-0.6	50
0.6-0.7	23
0.7-0.8	0
0.8-0.85	2
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8714	High Similarity	NPC58716
0.8169	Intermediate Similarity	NPC45618
0.8056	Intermediate Similarity	NPC146792
0.7195	Intermediate Similarity	NPC3583
0.7013	Intermediate Similarity	NPC245014
0.6753	Remote Similarity	NPC261866
0.6709	Remote Similarity	NPC201292
0.6667	Remote Similarity	NPC189142
0.6667	Remote Similarity	NPC77660
0.6582	Remote Similarity	NPC45638
0.641	Remote Similarity	NPC473043
0.6375	Remote Similarity	NPC84265
0.6341	Remote Similarity	NPC605067
0.6173	Remote Similarity	NPC186807
0.6173	Remote Similarity	NPC105025
0.6145	Remote Similarity	NPC22832
0.6145	Remote Similarity	NPC601144
0.6125	Remote Similarity	NPC58053
0.6125	Remote Similarity	NPC39360
0.6125	Remote Similarity	NPC29763
0.6125	Remote Similarity	NPC210003
0.6071	Remote Similarity	NPC602805
0.6049	Remote Similarity	NPC93337
0.6049	Remote Similarity	NPC168822
0.6049	Remote Similarity	NPC95090
0.6049	Remote Similarity	NPC27408
0.6024	Remote Similarity	NPC191306
0.6024	Remote Similarity	NPC609451
0.5882	Remote Similarity	NPC311830
0.5882	Remote Similarity	NPC607707
0.5843	Remote Similarity	NPC607513
0.5814	Remote Similarity	NPC469931
0.5765	Remote Similarity	NPC243930
0.5765	Remote Similarity	NPC601710
0.5732	Remote Similarity	NPC19388
0.5732	Remote Similarity	NPC240431
0.5732	Remote Similarity	NPC55786
0.5732	Remote Similarity	NPC143851
0.5647	Remote Similarity	NPC237435
0.5595	Remote Similarity	NPC610763
0.5591	Remote Similarity	NPC150767
0.5581	Remote Similarity	NPC43211
0.5542	Remote Similarity	NPC19709
0.5529	Remote Similarity	NPC117260
0.5517	Remote Similarity	NPC88023
0.5517	Remote Similarity	NPC309025
0.5476	Remote Similarity	NPC277205
0.5476	Remote Similarity	NPC37919
0.5476	Remote Similarity	NPC136042
0.5465	Remote Similarity	NPC488071
0.5412	Remote Similarity	NPC84362
0.5402	Remote Similarity	NPC284960
0.5357	Remote Similarity	NPC83283
0.5349	Remote Similarity	NPC222936
0.5342	Remote Similarity	NPC162313
0.5333	Remote Similarity	NPC8856
0.5294	Remote Similarity	NPC259152
0.5287	Remote Similarity	NPC285197
0.5233	Remote Similarity	NPC603655
0.5227	Remote Similarity	NPC115760
0.5227	Remote Similarity	NPC21666
0.5227	Remote Similarity	NPC486578
0.5217	Remote Similarity	NPC275454
0.5176	Remote Similarity	NPC289667
0.5176	Remote Similarity	NPC110349
0.5169	Remote Similarity	NPC605784
0.5155	Remote Similarity	NPC256760
0.5116	Remote Similarity	NPC145038
0.5116	Remote Similarity	NPC56077
0.5116	Remote Similarity	NPC297987
0.5116	Remote Similarity	NPC281131
0.5116	Remote Similarity	NPC253662
0.5116	Remote Similarity	NPC179950
0.5116	Remote Similarity	NPC88789
0.5116	Remote Similarity	NPC491374
0.5111	Remote Similarity	NPC190003
0.5109	Remote Similarity	NPC603300
0.5059	Remote Similarity	NPC331652

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC586408 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6127
0.1-0.2	2948
0.2-0.3	59
0.3-0.4	12
0.4-0.5	3
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
0.5647	Remote Similarity	NPD4338	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