NPASS Compound

Natural Product: NPC474388

Natural Product ID	NPC474388
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Rhamnazin Triacetate
IUPAC Name	[4-(3,5-diacetyloxy-7-methoxy-4-oxochromen-2-yl)-2-methoxyphenyl] acetate
Synonyms	Rhamnazin Triacetate
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL465819
PubChem CID	44584491
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0002585] O-methylated flavonoids [CHEMONTID:0002592] 7-O-methylated flavonoids

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 53 55 0 0 0 0 0 0 0 0999 V2000 -5.1084 4.1955 -1.8485 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7497 3.9271 -1.6348 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3486 2.6699 -1.1191 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3094 1.7290 -0.8357 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9094 0.5138 -0.3363 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7983 -0.5124 -0.0143 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1778 -1.4747 -0.9404 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6712 -1.3713 -2.1011 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1231 -2.5746 -0.6157 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5611 0.2288 -0.1171 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5952 1.1817 -0.4046 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0222 2.3945 -0.9054 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3194 0.9308 -0.2042 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1803 -0.1929 0.2680 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7371 -1.1568 0.5615 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1160 -0.9673 0.3773 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9478 -1.8471 0.6471 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3647 -2.3719 1.0499 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3739 -3.4535 0.1407 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7198 -3.2335 -1.0461 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0063 -4.8157 0.5414 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6268 -0.2921 0.4242 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2584 -1.3272 1.0385 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6596 -1.3007 1.0803 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4033 -0.2805 0.5314 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7500 0.7724 -0.0928 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4008 0.7533 -0.1372 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5394 1.7721 -0.6280 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9869 2.8954 -1.2882 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8001 -0.2892 0.5931 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4301 0.3080 1.6819 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6996 0.8298 2.5628 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9031 0.3525 1.8417 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4917 3.6057 -2.7107 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2410 5.2653 -2.0502 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7328 3.9477 -0.9574 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3492 1.9202 -0.9938 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1173 -2.2033 -0.3213 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1590 -3.2625 -1.4783 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7209 -3.1222 0.2716 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2778 3.1405 -1.1315 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7665 -4.8305 1.3584 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9147 -5.3550 0.8407 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4563 -5.3627 -0.3339 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7131 -2.1217 1.4874 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1295 -2.1315 1.5711 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9056 1.5975 -0.6369 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1080 2.6487 -1.9059 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7169 3.7144 -0.5925 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7636 3.3422 -1.9730 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2241 -0.4862 2.4617 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1638 1.3503 2.2878 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3652 0.3499 0.8252 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 6 7 1 0 7 8 2 0 7 9 1 0 5 10 2 0 10 11 1 0 11 12 2 0 11 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 15 18 1 0 18 19 1 0 19 20 2 0 19 21 1 0 14 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 1 0 25 30 1 0 30 31 1 0 31 32 2 0 31 33 1 0 12 3 1 0 27 22 1 0 16 10 1 0 1 34 1 0 1 35 1 0 1 36 1 0 4 37 1 0 9 38 1 0 9 39 1 0 9 40 1 0 12 41 1 0 21 42 1 0 21 43 1 0 21 44 1 0 23 45 1 0 24 46 1 0 27 47 1 0 29 48 1 0 29 49 1 0 29 50 1 0 33 51 1 0 33 52 1 0 33 53 1 0 M END

Standard InCHIKey	LODXNGWSMYYFFA-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C23H20O10/c1-11(24)30-16-7-6-14(8-17(16)29-5)22-23(32-13(3)26)21(27)20-18(31-12(2)25)9-15(28-4)10-19(20)33-22/h6-10H,1-5H3
SMILES	COc1cc(OC(=O)C)c2c(c1)oc(c(c2=O)OC(=O)C)c1ccc(c(c1)OC)OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	456.11	Volume:	439.596 ? Van der Waals volume.
Dense:	1.038	LogP:	2.105 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.486 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.719 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	21.0
TPSA:	127.57 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.403	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.579	Fsp³:	0.217
MCE-18:	22.0 ? 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:	0
Colloidal aggregators:	0.023	Fluc inhibitor:	0.327 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.989 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.787 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.341	Promiscuous compounds:	0.246

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.707	MDCK Permeability:	-4.383
Pgp-inhibitor:	0.999	Pgp-substrate:	0.005
PAMPA:	0.006 ? 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):	0.095
20% Bioavailability (F20%):	0.035	30% Bioavailability (F30%):	0.718
50% Bioavailability (F50%):	0.94

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.268
Plasma Protein Binding (PPB):	85.287%	Volume Distribution (VD):	-0.197
Fu:	18.107% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.05
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.422	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	0.128	CYP2C19-substrate:	0.923
CYP2C9-inhibitor:	0.019	CYP2C9-substrate:	0.017
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.034
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.973
HLM stability:	0.994 ? 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):

3.173

Half-life (T1/2):

0.443

ADMET: Toxicity

hERG Blockers:	0.005	hERG Blockers (10um):	0.106
Human Hepatotoxicity (H-HT):	0.357	Drug-induced Liver Injury (DILI):	0.985
AMES Toxicity:	0.54	Rat Oral Acute Toxicity:	0.691
Maximum Recommended Daily Dose:	0.244	Skin Sensitization:	0.903
Carcinogencity:	0.237	Eye Corrosion:	0.704
Eye Irritation:	0.906	Respiratory Toxicity:	0.226
Drug-induced Neurotoxicity:	0.143	Ototoxicity:	0.058
Hematotoxicity:	0.674	Drug-induced Nephrotoxicity:	0.021
Genotoxicity:	0.769	RPMI-8226 Immunitoxicity:	0.03
A549 Cytotoxicity:	0.775	Hek293 Cytotoxicity:	0.161
BCF:	0.763 ? 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:	3.813 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.849 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.546 ? 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
NPO33118	Rhamnus	Genus	Rhamnaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8350094]

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

Activity Type	# Activity
Activity	3

Activity Type	# Activity
Cell line	3

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
NPT20967	Cell line	Platelet	n.a.	Activity	=	10.0	%	PMID[8350094]
NPT20967	Cell line	Platelet	n.a.	Activity	=	14.3	%	PMID[8350094]
NPT20967	Cell line	Platelet	n.a.	Activity	=	84.5	%	PMID[8350094]

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 NPC474388 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	32305
0.1-0.2	15477
0.2-0.3	1704
0.3-0.4	282
0.4-0.5	57
0.5-0.6	17
0.6-0.7	5
0.7-0.8	0
0.8-0.85	0
0.85-0.9	2
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9615	High Similarity	NPC474170
0.8727	High Similarity	NPC472535
0.8704	High Similarity	NPC177839
0.7778	Intermediate Similarity	NPC310259
0.7193	Intermediate Similarity	NPC605569
0.7143	Intermediate Similarity	NPC474037
0.6833	Remote Similarity	NPC608137
0.6429	Remote Similarity	NPC72452
0.6316	Remote Similarity	NPC602291
0.629	Remote Similarity	NPC34725
0.6024	Remote Similarity	NPC475434
0.5902	Remote Similarity	NPC70853
0.5862	Remote Similarity	NPC61546
0.5833	Remote Similarity	NPC259058
0.5823	Remote Similarity	NPC475214
0.5738	Remote Similarity	NPC90582
0.5738	Remote Similarity	NPC299923
0.5714	Remote Similarity	NPC605582
0.5625	Remote Similarity	NPC179126
0.5625	Remote Similarity	NPC261548
0.5522	Remote Similarity	NPC122623
0.5476	Remote Similarity	NPC476180
0.5385	Remote Similarity	NPC236769
0.5362	Remote Similarity	NPC241774
0.5152	Remote Similarity	NPC104459
0.5139	Remote Similarity	NPC257277
0.5075	Remote Similarity	NPC279930
0.5075	Remote Similarity	NPC131557

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC474388 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5501
0.1-0.2	3589
0.2-0.3	56
0.3-0.4	3
0.4-0.5	1
0.5-0.6	0
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
		NPD

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