NPASS Compound

Natural Product: NPC319752

Natural Product ID	NPC319752
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Isocyclomulberrin
IUPAC Name	3,8,10-trihydroxy-9-(3-methylbut-2-enyl)-6-(2-methylprop-1-enyl)-6H-chromeno[4,3-b]chromen-7-one
Synonyms	Isocyclomulberrin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL485976
PubChem CID	5316260
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0003520] Pyranoflavonoids

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 55 58 0 0 0 0 0 0 0 0999 V2000 -5.0692 1.9725 0.4308 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3582 1.5270 -0.7695 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5920 0.4762 -0.8154 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3281 -0.4145 0.3264 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9807 -0.0792 1.4917 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3803 0.2135 2.7074 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1378 0.5821 3.8108 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4910 0.8613 4.9918 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2813 1.2268 6.0742 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1241 0.7994 5.1574 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3714 0.4314 4.0553 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0167 0.1521 2.8738 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2233 -0.2379 1.7062 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8611 -0.5149 0.5276 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0051 -0.8874 -0.5173 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4817 -1.1646 -1.6243 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3621 -0.9449 -0.3024 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9290 -0.6474 0.9173 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1012 -0.3072 1.8660 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2942 -0.7063 1.1213 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1669 -1.0719 0.0949 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6001 -1.3684 -1.1217 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2289 -1.3062 -1.3157 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6547 -1.6088 -2.5567 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -1.7633 -2.2636 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1591 -0.5977 -2.8495 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4625 -0.4542 -2.9862 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4088 -1.4874 -2.5510 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0365 0.7898 -3.6018 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5387 -1.1212 0.3338 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5095 2.3304 -2.0515 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7143 1.1998 0.8543 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7525 2.8347 0.1219 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3446 2.3587 1.1672 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1286 0.2608 -1.7999 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7171 -1.4387 0.0165 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2140 0.6395 3.7140 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4969 0.5074 6.7680 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6759 1.0339 6.1219 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3080 0.3652 4.1192 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7206 -0.4662 2.0993 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7618 -0.9900 -3.3500 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8111 -2.2639 -3.0398 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1745 -2.5320 -1.9598 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5166 0.2140 -3.1990 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1074 -2.0597 -1.6745 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4002 -1.0014 -2.3179 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6506 -2.1803 -3.4110 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2305 1.4055 -4.0154 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5600 1.3674 -2.8016 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8127 0.5590 -4.3565 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9652 -1.9165 0.8327 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9872 1.6945 -2.8354 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0918 3.2150 -1.8189 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4755 2.5139 -2.3956 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 1 0 6 7 2 0 7 8 1 0 8 9 1 0 8 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 15 17 1 0 17 18 2 0 18 19 1 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 22 25 1 0 25 26 1 0 26 27 2 3 27 28 1 0 27 29 1 0 21 30 1 0 2 31 1 0 14 4 1 0 23 17 1 0 12 6 1 0 19 13 1 0 1 32 1 0 1 33 1 0 1 34 1 0 3 35 1 0 4 36 1 0 7 37 1 0 9 38 1 0 10 39 1 0 11 40 1 0 20 41 1 0 24 42 1 0 25 43 1 0 25 44 1 0 26 45 1 0 28 46 1 0 28 47 1 0 28 48 1 0 29 49 1 0 29 50 1 0 29 51 1 0 30 52 1 0 31 53 1 0 31 54 1 0 31 55 1 0 M END

Standard InCHIKey	PWHGUSAQRRPLSJ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C25H24O6/c1-12(2)5-7-15-17(27)11-20-21(23(15)28)24(29)22-19(9-13(3)4)30-18-10-14(26)6-8-16(18)25(22)31-20/h5-6,8-11,19,26-28H,7H2,1-4H3
SMILES	CC(=CC1Oc2cc(O)ccc2c2c1c(=O)c1c(o2)cc(c(c1O)CC=C(C)C)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	420.16	Volume:	433.107 ? Van der Waals volume.
Dense:	0.97	LogP:	5.112 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.874 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.989 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	24.0
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:	0.485	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.8	Fsp³:	0.24
MCE-18:	79.677 ? 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:	0.948	Fluc inhibitor:	0.394 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.915 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.91 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.232	Promiscuous compounds:	0.078

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.115	MDCK Permeability:	-4.768
Pgp-inhibitor:	0.184	Pgp-substrate:	0.228
PAMPA:	0.585 ? 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):	0.032
20% Bioavailability (F20%):	0.953	30% Bioavailability (F30%):	0.995
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.01	MRP1:	0.923
Plasma Protein Binding (PPB):	94.375%	Volume Distribution (VD):	0.217
Fu:	7.217% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.885	BCRP inhibitor:	0.856
BSEP inhibitor:	0.93

ADMET: Metabolism

CYP1A2-inhibitor:	0.018	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.973	CYP2C19-substrate:	0.999
CYP2C9-inhibitor:	0.43	CYP2C9-substrate:	0.472
CYP2D6-inhibitor:	0.917	CYP2D6-substrate:	0.992
CYP3A4-inhibitor:	0.906	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):

3.21

Half-life (T1/2):

1.54

ADMET: Toxicity

hERG Blockers:	0.036	hERG Blockers (10um):	0.584
Human Hepatotoxicity (H-HT):	0.647	Drug-induced Liver Injury (DILI):	0.788
AMES Toxicity:	0.751	Rat Oral Acute Toxicity:	0.787
Maximum Recommended Daily Dose:	0.793	Skin Sensitization:	0.971
Carcinogencity:	0.737	Eye Corrosion:	0.003
Eye Irritation:	0.946	Respiratory Toxicity:	0.958
Drug-induced Neurotoxicity:	0.069	Ototoxicity:	0.218
Hematotoxicity:	0.108	Drug-induced Nephrotoxicity:	0.154
Genotoxicity:	0.973	RPMI-8226 Immunitoxicity:	0.073
A549 Cytotoxicity:	0.422	Hek293 Cytotoxicity:	0.812
BCF:	1.721 ? 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:	4.752 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.232 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.718 ? 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
NPO27239	Maclura tinctoria	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11087602]
NPO27239	Maclura tinctoria	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12932124]
NPO27239	Maclura tinctoria	Species	Moraceae	Eukaryota	n.a.	stem	n.a.	PMID[12932124]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20815207]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	root	n.a.	PMID[21319773]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	bark	n.a.	PMID[21319773]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	leaf	n.a.	PMID[21319773]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	leaf	n.a.	PMID[22207282]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	root	n.a.	PMID[23806866]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	root bark	University of Veterinary and Pharmaceutical Sciences Brno (UVPS Brno), Brno, Czech Republic	2011-APR	PMID[24901948]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	Konya, Turkey	2007-APR	PMID[24901948]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	leaves	Chungbuk, Korea	n.a.	PMID[25935644]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	root	n.a.	PMID[25981820]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	latex	n.a.	PMID[27294120]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	Root barks	n.a.	n.a.	PMID[3097265]
NPO27239	Maclura tinctoria	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO28265	Morus alba	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27239	Maclura tinctoria	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
FC	1
EC50	1
IC50	1

Activity Type	# Activity
Individual protein	1
Cell line	1
Organism	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1651	Individual protein	Nuclear factor erythroid 2-related factor 2	Mus musculus	FC	=	1.31	n.a.	PMID[30227999]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT315	Cell line	CEM-SS	Homo sapiens	IC50	=	17.0	ug.mL-1	PMID[11087602]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	7.5	ug.mL-1	PMID[11087602]

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 NPC319752 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	23597
0.1-0.2	22367
0.2-0.3	3434
0.3-0.4	375
0.4-0.5	64
0.5-0.6	14
0.6-0.7	4
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
0.6761	Remote Similarity	NPC599988
0.6623	Remote Similarity	NPC476088
0.6456	Remote Similarity	NPC321623
0.6026	Remote Similarity	NPC469658
0.5946	Remote Similarity	NPC303633
0.5926	Remote Similarity	NPC474161
0.5811	Remote Similarity	NPC306488
0.5789	Remote Similarity	NPC608191
0.5694	Remote Similarity	NPC24821
0.5542	Remote Similarity	NPC189087
0.5542	Remote Similarity	NPC603859
0.5479	Remote Similarity	NPC284220
0.5342	Remote Similarity	NPC114377
0.527	Remote Similarity	NPC157784
0.5263	Remote Similarity	NPC55018
0.5195	Remote Similarity	NPC482761
0.5125	Remote Similarity	NPC602497
0.5062	Remote Similarity	NPC212932

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC319752 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4198
0.1-0.2	4895
0.2-0.3	56
0.3-0.4	1
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