NPASS Compound

Natural Product: NPC568145

Natural Product ID	NPC568145
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	1-hydroxy-2-methyl-3-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-anthracene-9,10-dione
IUPAC Name	1-hydroxy-2-methyl-3-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-anthracene-9,10-dione
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 50 53 0 0 0 0 0 0 0 0999 V2000 0.3212 2.0115 -2.8147 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9796 1.1990 -1.7417 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1902 0.5958 -0.7833 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1196 0.7456 -0.8303 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2188 0.3606 -0.1430 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9820 -0.4343 -0.9594 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2039 -0.8097 -0.5317 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.2255 -0.3654 -1.5845 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5120 -0.7425 -1.1668 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6188 -0.4467 0.8416 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.5277 -1.5675 1.7006 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9776 0.7447 1.4511 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.8620 1.6226 2.0622 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0891 1.4382 0.4368 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3818 2.4111 1.1131 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8401 -0.1433 0.1857 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2249 -0.2698 0.1903 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8926 -1.0664 1.2386 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1676 -1.6092 2.1027 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3448 -1.2215 1.2751 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9358 -1.9744 2.2706 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3148 -2.0822 2.2491 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0876 -1.4659 1.2749 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4521 -0.7207 0.2959 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0812 -0.5950 0.2908 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4336 0.1967 -0.7532 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0905 0.7703 -1.6524 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9837 0.3460 -0.7819 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3473 1.0949 -1.7667 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1424 1.6935 -2.7185 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0169 2.9689 -2.3728 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5825 1.4974 -3.2056 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0031 2.2142 -3.6505 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9009 -0.2820 0.7321 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2391 -1.9408 -0.5973 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0513 -0.8830 -2.5499 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1545 0.7185 -1.7895 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4535 -1.5457 -0.5720 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7293 -0.2326 0.8065 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4469 -2.3726 1.1305 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2730 0.3723 2.2523 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9737 1.3550 3.0073 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6938 1.9649 -0.3420 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4801 2.1574 1.3852 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3099 -0.6533 0.9785 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3231 -2.4360 3.0048 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8350 -2.6509 2.9912 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1639 -1.5788 1.2998 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0125 -0.2260 -0.4785 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2367 2.6959 -2.7810 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 7 10 1 0 10 11 1 0 10 12 1 0 12 13 1 0 12 14 1 0 14 15 1 0 3 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 26 28 1 0 28 29 2 0 29 30 1 0 29 2 1 0 14 5 1 0 28 17 1 0 25 20 1 0 1 31 1 0 1 32 1 0 1 33 1 0 5 34 1 1 7 35 1 1 8 36 1 0 8 37 1 0 9 38 1 0 10 39 1 6 11 40 1 0 12 41 1 1 13 42 1 0 14 43 1 6 15 44 1 0 16 45 1 0 21 46 1 0 22 47 1 0 23 48 1 0 24 49 1 0 30 50 1 0 M END

Standard InCHIKey	YSFFDJHGFBRUBX-PTKNJCLRSA-N
Standard InCHI	InChI=1S/C21H20O9/c1-8-12(29-21-20(28)19(27)18(26)13(7-22)30-21)6-11-14(15(8)23)17(25)10-5-3-2-4-9(10)16(11)24/h2-6,13,18-23,26-28H,7H2,1H3/t13-,18-,19+,20-,21-/m1/s1
SMILES	CC1=C(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)C=C2C(=O)C3=CC=CC=C3C(=O)C2=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	416.11	Volume:	395.567 ? Van der Waals volume.
Dense:	1.052	LogP:	1.998 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.307 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.447 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	24.0
TPSA:	153.75 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.386	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.742	Fsp³:	0.333
MCE-18:	87.286 ? 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:	0	PAINS Alert:	1
Colloidal aggregators:	0.468	Fluc inhibitor:	0.265 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.384 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.513 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.127	Promiscuous compounds:	0.345

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.194	MDCK Permeability:	-5.185
Pgp-inhibitor:	0.126	Pgp-substrate:	0.025
PAMPA:	0.995 ? 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):	0.901
20% Bioavailability (F20%):	0.006	30% Bioavailability (F30%):	0.963
50% Bioavailability (F50%):	0.941

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.179
Plasma Protein Binding (PPB):	93.681%	Volume Distribution (VD):	0.083
Fu:	5.459% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.026
BSEP inhibitor:	0.003

ADMET: Metabolism

CYP1A2-inhibitor:	0.789	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	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:	0.535
HLM stability:	0.019 ? 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):

2.575

Half-life (T1/2):

3.27

ADMET: Toxicity

hERG Blockers:	0.017	hERG Blockers (10um):	0.165
Human Hepatotoxicity (H-HT):	0.824	Drug-induced Liver Injury (DILI):	0.975
AMES Toxicity:	0.972	Rat Oral Acute Toxicity:	0.05
Maximum Recommended Daily Dose:	0.035	Skin Sensitization:	0.997
Carcinogencity:	0.576	Eye Corrosion:	0.0
Eye Irritation:	0.58	Respiratory Toxicity:	0.048
Drug-induced Neurotoxicity:	0.027	Ototoxicity:	0.913
Hematotoxicity:	0.766	Drug-induced Nephrotoxicity:	0.803
Genotoxicity:	0.798	RPMI-8226 Immunitoxicity:	0.189
A549 Cytotoxicity:	0.752	Hek293 Cytotoxicity:	0.345
BCF:	0.661 ? 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:	3.317 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.905 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.092 ? 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
NPO62375	Caelospermum reticulatum	Genus	Rubiaceae	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 NPC568145 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	13368
0.1-0.2	30892
0.2-0.3	4556
0.3-0.4	736
0.4-0.5	239
0.5-0.6	44
0.6-0.7	8
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
0.8276	Intermediate Similarity	NPC610808
0.7586	Intermediate Similarity	NPC222455
0.6923	Remote Similarity	NPC605700
0.6667	Remote Similarity	NPC603035
0.6471	Remote Similarity	NPC606202
0.6418	Remote Similarity	NPC146837
0.6212	Remote Similarity	NPC600107
0.6176	Remote Similarity	NPC278329
0.6154	Remote Similarity	NPC134260
0.6	Remote Similarity	NPC212099
0.5942	Remote Similarity	NPC30432
0.5932	Remote Similarity	NPC608788
0.5867	Remote Similarity	NPC475246
0.5857	Remote Similarity	NPC101116
0.5821	Remote Similarity	NPC111536
0.5714	Remote Similarity	NPC5029
0.5667	Remote Similarity	NPC226712
0.5658	Remote Similarity	NPC605677
0.5652	Remote Similarity	NPC210192
0.56	Remote Similarity	NPC3718
0.5556	Remote Similarity	NPC199357
0.5556	Remote Similarity	NPC76128
0.5507	Remote Similarity	NPC604892
0.5493	Remote Similarity	NPC271385
0.5455	Remote Similarity	NPC599943
0.5455	Remote Similarity	NPC606287
0.5417	Remote Similarity	NPC212290
0.5385	Remote Similarity	NPC605952
0.5316	Remote Similarity	NPC610785
0.5309	Remote Similarity	NPC475161
0.5294	Remote Similarity	NPC475628
0.5278	Remote Similarity	NPC606849
0.5238	Remote Similarity	NPC214454
0.5231	Remote Similarity	NPC205054
0.5231	Remote Similarity	NPC23084
0.5224	Remote Similarity	NPC106025
0.5211	Remote Similarity	NPC302989
0.5195	Remote Similarity	NPC603889
0.5179	Remote Similarity	NPC228907
0.5167	Remote Similarity	NPC294470
0.5161	Remote Similarity	NPC12308
0.5156	Remote Similarity	NPC40377
0.5139	Remote Similarity	NPC99233
0.5128	Remote Similarity	NPC607703
0.5085	Remote Similarity	NPC212729
0.5085	Remote Similarity	NPC142319
0.5085	Remote Similarity	NPC604498
0.5082	Remote Similarity	NPC9248
0.5082	Remote Similarity	NPC152722
0.5077	Remote Similarity	NPC218685
0.5072	Remote Similarity	NPC199335
0.5072	Remote Similarity	NPC477240
0.507	Remote Similarity	NPC146803
0.5067	Remote Similarity	NPC61594

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC568145 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3101
0.1-0.2	5803
0.2-0.3	234
0.3-0.4	9
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
0.5667	Remote Similarity	NPD1091	Pre-clinical

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