NPASS Compound

Natural Product: NPC321896

Natural Product ID	NPC321896
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Nigrasin H
IUPAC Name	(8R)-2-(2,4-dihydroxyphenyl)-5-hydroxy-8,9,9-trimethyl-3-(3-methylbut-2-enyl)-8H-furo[2,3-h]chromen-4-one
Synonyms	nigrasin H
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1773618
PubChem CID	54583211
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001615] Flavones [CHEMONTID:0003501] 3-prenylated flavones

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 57 60 0 0 0 0 0 0 0 0999 V2000 -5.3402 -1.2724 -0.0982 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6002 -0.7736 -1.3190 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4862 -0.0709 -1.1768 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9692 0.2180 0.2386 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5327 -0.1669 0.2907 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5566 0.6852 0.6128 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7061 0.2830 0.3545 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0065 -0.8646 -0.1714 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0320 -1.7811 -0.5146 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2739 -1.4397 -0.2839 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1968 -2.2348 -0.5779 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3632 -3.0185 -1.0862 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6786 -3.8826 -1.4032 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6767 -3.3573 -1.3209 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6477 -2.4432 -0.9755 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3257 -1.2096 -0.4066 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6186 -0.5525 -0.1427 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9901 -0.8496 1.3030 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6948 0.8940 -0.4724 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5742 -1.2693 -1.1024 C 0 0 2 0 0 0 0 0 0 0 0 0 4.0164 -2.5581 -1.1109 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9862 -1.2154 -0.5982 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7471 1.9990 1.2169 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1824 2.9928 0.8384 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2224 4.2206 1.3710 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7069 4.5348 2.3531 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6189 3.5939 2.7406 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6365 2.3372 2.1794 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6033 1.4123 2.6480 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6766 5.7872 2.9044 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2030 -1.1348 -2.6248 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7182 -2.0002 0.4067 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5130 -0.4085 0.6015 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3477 -1.6209 -0.3606 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9389 0.2972 -1.9876 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5357 -0.4016 0.9128 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1099 1.3256 0.3411 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5455 -4.4428 -2.2582 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8771 -4.3247 -1.7635 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5942 -0.0535 1.7485 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4765 -1.8602 1.3783 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0429 -0.9666 1.8896 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2686 1.0944 -1.4346 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7471 1.4268 -0.4641 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3374 1.3836 0.3077 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4273 -0.8240 -2.1057 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9500 -0.8074 0.4520 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4610 -2.2143 -0.5754 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5632 -0.4629 -1.1864 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9127 2.7488 0.0552 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9585 4.9545 1.0593 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3602 3.8021 3.4991 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5540 1.8223 2.6262 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1880 6.5913 2.5110 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2531 -1.5070 -2.4957 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1314 -0.3668 -3.3890 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6371 -2.0483 -2.9652 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 9 12 1 0 12 13 1 0 12 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 17 19 1 0 17 20 1 0 20 21 1 0 20 22 1 0 6 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 26 30 1 0 2 31 1 0 10 5 1 0 21 15 1 0 28 23 1 0 16 8 1 0 1 32 1 0 1 33 1 0 1 34 1 0 3 35 1 0 4 36 1 0 4 37 1 0 13 38 1 0 14 39 1 0 18 40 1 0 18 41 1 0 18 42 1 0 19 43 1 0 19 44 1 0 19 45 1 0 20 46 1 6 22 47 1 0 22 48 1 0 22 49 1 0 24 50 1 0 25 51 1 0 27 52 1 0 29 53 1 0 30 54 1 0 31 55 1 0 31 56 1 0 31 57 1 0 M END

Standard InCHIKey	FJZJTEHPYMIMST-CYBMUJFWSA-N
Standard InCHI	InChI=1S/C25H26O6/c1-12(2)6-8-16-22(29)20-18(28)11-19-21(25(4,5)13(3)30-19)24(20)31-23(16)15-9-7-14(26)10-17(15)27/h6-7,9-11,13,26-28H,8H2,1-5H3/t13-/m1/s1
SMILES	CC(=CCc1c(oc2c(c1=O)c(O)cc1c2C(C)(C)[C@H](O1)C)c1ccc(cc1O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	422.17	Volume:	435.743 ? Van der Waals volume.
Dense:	0.969	LogP:	4.598 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.536 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.116 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	23.0
TPSA:	100.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.505	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.772	Fsp³:	0.32
MCE-18:	87.394 ? 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:	0.871	Fluc inhibitor:	0.371 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.927 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.813 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.201	Promiscuous compounds:	0.127

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.026	MDCK Permeability:	-4.826
Pgp-inhibitor:	0.818	Pgp-substrate:	0.532
PAMPA:	0.401 ? 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):	0.031
20% Bioavailability (F20%):	0.944	30% Bioavailability (F30%):	0.994
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.969
Plasma Protein Binding (PPB):	95.926%	Volume Distribution (VD):	0.332
Fu:	4.204% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.868	BCRP inhibitor:	0.92
BSEP inhibitor:	0.938

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.996	CYP2C19-substrate:	0.999
CYP2C9-inhibitor:	0.004	CYP2C9-substrate:	0.429
CYP2D6-inhibitor:	0.081	CYP2D6-substrate:	0.709
CYP3A4-inhibitor:	0.476	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

2.015

Half-life (T1/2):

1.768

ADMET: Toxicity

hERG Blockers:	0.043	hERG Blockers (10um):	0.48
Human Hepatotoxicity (H-HT):	0.538	Drug-induced Liver Injury (DILI):	0.78
AMES Toxicity:	0.659	Rat Oral Acute Toxicity:	0.823
Maximum Recommended Daily Dose:	0.87	Skin Sensitization:	0.921
Carcinogencity:	0.529	Eye Corrosion:	0.0
Eye Irritation:	0.778	Respiratory Toxicity:	0.942
Drug-induced Neurotoxicity:	0.212	Ototoxicity:	0.274
Hematotoxicity:	0.122	Drug-induced Nephrotoxicity:	0.391
Genotoxicity:	0.997	RPMI-8226 Immunitoxicity:	0.063
A549 Cytotoxicity:	0.514	Hek293 Cytotoxicity:	0.782
BCF:	1.775 ? 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:	4.841 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.354 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.84 ? 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
NPO19738	Morus nigra	Species	Moraceae	Eukaryota	n.a.	bark	n.a.	PMID[18330242]
NPO19738	Morus nigra	Species	Moraceae	Eukaryota	n.a.	twig	n.a.	PMID[21401118]
NPO19738	Morus nigra	Species	Moraceae	Eukaryota	twigs	Xinjiang Uygur Autonomous Region, China	2006-MAY	PMID[21401118]
NPO19738	Morus nigra	Species	Moraceae	Eukaryota	root bark	Konya, Turkey	2007-APR	PMID[24901948]
NPO19738	Morus nigra	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[34663156]
NPO19738	Morus nigra	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[35848720]
NPO19738	Morus nigra	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36829941]
NPO19738	Morus nigra	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19738	Morus nigra	Species	Moraceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO19738	Morus nigra	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

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
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	203.39	%	PMID[21401118]
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	143.94	%	PMID[21401118]
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	102.16	%	PMID[21401118]

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 NPC321896 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	22385
0.1-0.2	24356
0.2-0.3	2855
0.3-0.4	222
0.4-0.5	21
0.5-0.6	14
0.6-0.7	3
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
0.6709	Remote Similarity	NPC62840
0.6528	Remote Similarity	NPC96565
0.6486	Remote Similarity	NPC11700
0.5946	Remote Similarity	NPC190046
0.5844	Remote Similarity	NPC607385
0.5806	Remote Similarity	NPC195846
0.5732	Remote Similarity	NPC77856
0.5513	Remote Similarity	NPC303633
0.5476	Remote Similarity	NPC282300
0.5412	Remote Similarity	NPC219915
0.5412	Remote Similarity	NPC78803
0.5375	Remote Similarity	NPC241100
0.5294	Remote Similarity	NPC187354
0.5227	Remote Similarity	NPC217083
0.5181	Remote Similarity	NPC473286
0.5172	Remote Similarity	NPC276444
0.5119	Remote Similarity	NPC13408

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC321896 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3975
0.1-0.2	5134
0.2-0.3	39
0.3-0.4	2
0.4-0.5	0
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