NPASS Compound

Natural Product: NPC160821

Natural Product ID	NPC160821
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Lespeflorin A3
IUPAC Name	(2S)-2-(2,2-dimethylchromen-6-yl)-7-hydroxy-6,8-bis(3-methylbut-2-enyl)-2,3-dihydrochromen-4-one
Synonyms	Lespeflorin A3
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL550552
PubChem CID	25243166
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0003642] 8-prenylated flavans [CHEMONTID:0003508] 8-prenylated flavanones

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 68 71 0 0 0 0 0 0 0 0999 V2000 -6.9770 -1.5929 -0.4935 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6447 -1.6295 0.9520 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4428 -2.0135 1.3382 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3307 -2.4310 0.4734 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1240 -1.5671 0.7004 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0696 -2.0337 1.4372 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9685 -1.2523 1.6520 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1685 -1.7376 2.4450 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3727 -2.9842 2.5289 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0147 -0.7336 3.1042 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1926 0.5384 2.3390 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5642 0.5449 1.7354 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6035 1.2193 2.3434 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8833 1.2257 1.7887 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1541 0.5577 0.6129 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1197 -0.1169 0.0029 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4328 -0.8197 -1.2349 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6288 -0.8454 -1.7919 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7400 -0.1315 -1.1511 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2833 0.8792 -2.1459 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8011 -1.1677 -0.8191 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4086 0.5338 0.0209 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8557 -0.1165 0.5609 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2124 0.7830 1.3576 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8990 0.0133 1.1332 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9513 0.5366 0.3724 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8446 1.9102 -0.1751 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9562 2.0032 -1.3370 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3928 2.4493 -2.4859 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8044 2.8719 -2.6325 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4706 2.5305 -3.6418 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0421 -0.2848 0.1809 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0929 0.2018 -0.5619 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6774 -1.2318 1.9323 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5752 -2.4534 -1.0630 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6563 -0.6462 -0.9976 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1039 -1.6546 -0.6129 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2292 -2.0300 2.4258 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0763 -3.5013 0.5662 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6211 -2.2790 -0.5871 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1062 -3.0277 1.8520 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0061 -1.1997 3.2760 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6237 -0.5199 4.1437 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1700 1.3805 3.0675 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4084 1.7433 3.2576 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7040 1.7551 2.2641 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6377 -1.3579 -1.7361 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8358 -1.3809 -2.7200 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3977 1.3128 -2.6642 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9700 0.3566 -2.8447 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7807 1.6846 -1.5678 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3320 -1.5037 -1.7105 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5051 -0.7857 -0.0669 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2953 -2.0721 -0.3782 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0401 -0.6567 0.0669 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4402 2.5807 0.6314 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8878 2.2412 -0.4573 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0750 1.6982 -1.2406 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9523 3.3459 -3.6299 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0771 3.6874 -1.8989 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5247 2.0659 -2.4692 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0316 2.5804 -4.5968 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1055 1.5626 -3.6623 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2547 3.3591 -3.5317 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7251 0.9324 -0.2184 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7862 -0.1196 1.9965 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4202 -1.5952 2.9518 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6754 -1.6122 1.6133 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 8 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 19 21 1 0 19 22 1 0 16 23 2 0 11 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 2 3 29 30 1 0 29 31 1 0 26 32 2 0 32 33 1 0 2 34 1 0 32 5 1 0 25 7 2 0 23 12 1 0 22 15 1 0 1 35 1 0 1 36 1 0 1 37 1 0 3 38 1 0 4 39 1 0 4 40 1 0 6 41 1 0 10 42 1 0 10 43 1 0 11 44 1 1 13 45 1 0 14 46 1 0 17 47 1 0 18 48 1 0 20 49 1 0 20 50 1 0 20 51 1 0 21 52 1 0 21 53 1 0 21 54 1 0 23 55 1 0 27 56 1 0 27 57 1 0 28 58 1 0 30 59 1 0 30 60 1 0 30 61 1 0 31 62 1 0 31 63 1 0 31 64 1 0 33 65 1 0 34 66 1 0 34 67 1 0 34 68 1 0 M END

Standard InCHIKey	SAZBMMMZQLNWMN-MHZLTWQESA-N
Standard InCHI	InChI=1S/C30H34O4/c1-18(2)7-9-22-16-24-25(31)17-27(33-29(24)23(28(22)32)11-8-19(3)4)20-10-12-26-21(15-20)13-14-30(5,6)34-26/h7-8,10,12-16,27,32H,9,11,17H2,1-6H3/t27-/m0/s1
SMILES	CC(=CCc1cc2C(=O)C[C@@H](c3ccc4c(C=CC(C)(C)O4)c3)Oc2c(CC=C(C)C)c1O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	458.25	Volume:	502.006 ? Van der Waals volume.
Dense:	0.913	LogP:	7.312 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.813 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.899 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	25.0
TPSA:	55.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.478	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.816	Fsp³:	0.367
MCE-18:	84.951 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.999	Fluc inhibitor:	0.789 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.741 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.607 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.311	Promiscuous compounds:	0.187

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.907	MDCK Permeability:	-4.683
Pgp-inhibitor:	0.928	Pgp-substrate:	0.005
PAMPA:	0.268 ? 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):	0.05
20% Bioavailability (F20%):	0.999	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.916
Plasma Protein Binding (PPB):	96.868%	Volume Distribution (VD):	0.4
Fu:	2.897% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.961
OATP1B3 inhibitor:	0.884	BCRP inhibitor:	0.999
BSEP inhibitor:	0.956

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.929	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.02
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.08
CYP3A4-inhibitor:	0.052	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.006	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):

7.838

Half-life (T1/2):

0.798

ADMET: Toxicity

hERG Blockers:	0.138	hERG Blockers (10um):	0.495
Human Hepatotoxicity (H-HT):	0.884	Drug-induced Liver Injury (DILI):	0.892
AMES Toxicity:	0.876	Rat Oral Acute Toxicity:	0.97
Maximum Recommended Daily Dose:	0.891	Skin Sensitization:	0.963
Carcinogencity:	0.709	Eye Corrosion:	0.0
Eye Irritation:	0.152	Respiratory Toxicity:	0.988
Drug-induced Neurotoxicity:	0.945	Ototoxicity:	0.812
Hematotoxicity:	0.545	Drug-induced Nephrotoxicity:	0.977
Genotoxicity:	0.996	RPMI-8226 Immunitoxicity:	0.155
A549 Cytotoxicity:	0.801	Hek293 Cytotoxicity:	0.584
BCF:	2.13 ? 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:	5.475 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	7.878 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	7.566 ? 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
NPO13293	Lespedeza floribunda	Species	Fabaceae	Eukaryota	roots	n.a.	n.a.	PMID[19132934]
NPO13293	Lespedeza floribunda	Species	Fabaceae	Eukaryota	n.a.	root	n.a.	PMID[19132934]
NPO13293	Lespedeza floribunda	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13293	Lespedeza floribunda	Species	Fabaceae	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
IC50	1

Activity Type	# Activity
Others	1

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
NPT2	Others	Unspecified	n.a.	IC50	=	1500.0	nM	PMID[19132934]

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 NPC160821 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	20681
0.1-0.2	26229
0.2-0.3	2405
0.3-0.4	415
0.4-0.5	100
0.5-0.6	19
0.6-0.7	7
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
0.8	Intermediate Similarity	NPC101793
0.6912	Remote Similarity	NPC197252
0.6765	Remote Similarity	NPC75049
0.6667	Remote Similarity	NPC310130
0.6575	Remote Similarity	NPC39752
0.6377	Remote Similarity	NPC59522
0.6282	Remote Similarity	NPC132592
0.6164	Remote Similarity	NPC23728
0.5867	Remote Similarity	NPC312973
0.5802	Remote Similarity	NPC283234
0.575	Remote Similarity	NPC110303
0.575	Remote Similarity	NPC601247
0.575	Remote Similarity	NPC609256
0.5714	Remote Similarity	NPC246948
0.5694	Remote Similarity	NPC236766
0.5694	Remote Similarity	NPC150408
0.5556	Remote Similarity	NPC192686
0.5556	Remote Similarity	NPC284820
0.5366	Remote Similarity	NPC111786
0.5309	Remote Similarity	NPC214774
0.5301	Remote Similarity	NPC119209
0.5195	Remote Similarity	NPC608140
0.5181	Remote Similarity	NPC54577
0.5135	Remote Similarity	NPC164980
0.5125	Remote Similarity	NPC142405
0.5122	Remote Similarity	NPC267375
0.5122	Remote Similarity	NPC40033

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC160821 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3343
0.1-0.2	5745
0.2-0.3	57
0.3-0.4	5
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