NPASS Compound

Natural Product: NPC482487

Natural Product ID	NPC482487
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KZDDYSMOBDHKFT-LLVKDONJSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
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 39 41 0 0 0 0 0 0 0 0999 V2000 5.0076 -1.6123 0.4474 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4253 -0.6420 -0.4179 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0496 -0.3759 -0.2844 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1254 -1.1016 -1.0160 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7923 -0.8317 -0.8757 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2518 -1.5410 -1.6019 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0759 -2.5403 -2.2893 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6534 -1.0718 -1.5120 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8933 -0.6139 -0.1005 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.2574 -0.0998 0.1259 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6887 1.1206 -0.3479 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9737 1.5839 -0.1238 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8842 0.8349 0.5904 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4623 -0.3870 1.0684 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1754 -0.8421 0.8394 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9616 0.4501 0.1505 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4028 0.1774 0.0101 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3410 0.8974 0.7377 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6884 0.6121 0.5845 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5902 1.3525 1.3278 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1250 2.5481 0.8138 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8956 1.8855 1.6001 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5342 -2.1055 -1.8957 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8403 -2.6131 -0.0052 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4957 -1.5977 1.4362 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0736 -1.4087 0.6422 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7523 -0.2329 -2.2413 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3605 -1.8681 -1.8055 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6319 -1.4474 0.5767 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9581 1.6994 -0.9096 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2662 2.5524 -0.5178 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8982 1.1970 0.7690 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1925 -0.9682 1.6311 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8609 -1.8174 1.2289 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8958 2.2714 0.0556 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5772 3.1764 1.6120 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3185 3.1124 0.2927 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4736 2.3159 2.2930 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3942 -2.0693 -2.8888 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 2 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 9 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 18 22 1 0 4 23 1 0 19 3 1 0 17 5 2 0 15 10 1 0 1 24 1 0 1 25 1 0 1 26 1 0 8 27 1 0 8 28 1 0 9 29 1 1 11 30 1 0 12 31 1 0 13 32 1 0 14 33 1 0 15 34 1 0 21 35 1 0 21 36 1 0 21 37 1 0 22 38 1 0 23 39 1 0 M END

Standard InCHIKey	KZDDYSMOBDHKFT-LLVKDONJSA-N
Standard InCHI	InChI=1S/C17H16O6/c1-21-16-13(19)12-10(18)8-11(9-6-4-3-5-7-9)23-15(12)14(20)17(16)22-2/h3-7,11,19-20H,8H2,1-2H3/t11-/m1/s1
SMILES	COc1c(c2C(=O)C[C@H](c3ccccc3)Oc2c(c1OC)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	316.09	Volume:	311.205 ? Van der Waals volume.
Dense:	1.016	LogP:	3.091 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.009 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.364 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	18.0
TPSA:	85.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.847	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.025	Fsp³:	0.235
MCE-18:	57.429 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.384	Fluc inhibitor:	0.46 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.283 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.289 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.297	Promiscuous compounds:	0.042

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.995	MDCK Permeability:	-4.775
Pgp-inhibitor:	0.292	Pgp-substrate:	0.045
PAMPA:	0.606 ? 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):	0.001
20% Bioavailability (F20%):	0.006	30% Bioavailability (F30%):	0.222
50% Bioavailability (F50%):	0.814

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.276	MRP1:	0.998
Plasma Protein Binding (PPB):	98.59%	Volume Distribution (VD):	-0.462
Fu:	0.856% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.25
OATP1B3 inhibitor:	0.826	BCRP inhibitor:	0.403
BSEP inhibitor:	0.615

ADMET: Metabolism

CYP1A2-inhibitor:	0.004	CYP1A2-substrate:	0.833
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.968
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.27	CYP3A4-substrate:	0.267
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.383
HLM stability:	0.887 ? 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):

7.291

Half-life (T1/2):

1.193

ADMET: Toxicity

hERG Blockers:	0.143	hERG Blockers (10um):	0.52
Human Hepatotoxicity (H-HT):	0.813	Drug-induced Liver Injury (DILI):	0.662
AMES Toxicity:	0.499	Rat Oral Acute Toxicity:	0.699
Maximum Recommended Daily Dose:	0.569	Skin Sensitization:	0.929
Carcinogencity:	0.315	Eye Corrosion:	0.108
Eye Irritation:	0.971	Respiratory Toxicity:	0.804
Drug-induced Neurotoxicity:	0.875	Ototoxicity:	0.356
Hematotoxicity:	0.388	Drug-induced Nephrotoxicity:	0.753
Genotoxicity:	0.717	RPMI-8226 Immunitoxicity:	0.159
A549 Cytotoxicity:	0.597	Hek293 Cytotoxicity:	0.387
BCF:	1.2 ? 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:	3.927 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.226 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.6 ? 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
NPO23434	Fissistigma latifolium	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29160716]
NPO23434	Fissistigma latifolium	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23434	Fissistigma latifolium	Species	Annonaceae	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
Ki	2

Activity Type	# Activity
Protein-protein interaction	2

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
NPT21617	Protein-protein interaction	Induced myeloid leukemia cell differentiation protein Mcl-1/BH3-interacting domain death agonist	Homo sapiens	Ki	>	33000.0	nM	PMID[29160716]
NPT21616	Protein-protein interaction	Bcl-xL/BAK	Homo sapiens	Ki	>	23000.0	nM	PMID[29160716]

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 NPC482487 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	23543
0.1-0.2	22384
0.2-0.3	3461
0.3-0.4	345
0.4-0.5	85
0.5-0.6	35
0.6-0.7	2
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
0.6154	Remote Similarity	NPC255106
0.6154	Remote Similarity	NPC235165
0.5962	Remote Similarity	NPC150648
0.5962	Remote Similarity	NPC37392
0.5862	Remote Similarity	NPC95936
0.5849	Remote Similarity	NPC194432
0.5849	Remote Similarity	NPC215885
0.5849	Remote Similarity	NPC110038
0.5686	Remote Similarity	NPC265871
0.5686	Remote Similarity	NPC205093
0.566	Remote Similarity	NPC162869
0.5636	Remote Similarity	NPC2416
0.5577	Remote Similarity	NPC213322
0.5472	Remote Similarity	NPC248372
0.5472	Remote Similarity	NPC243083
0.5472	Remote Similarity	NPC13768
0.5472	Remote Similarity	NPC482121
0.5472	Remote Similarity	NPC287246
0.5472	Remote Similarity	NPC204515
0.5472	Remote Similarity	NPC270964
0.5455	Remote Similarity	NPC475267
0.537	Remote Similarity	NPC312391
0.537	Remote Similarity	NPC177354
0.5333	Remote Similarity	NPC250214
0.5306	Remote Similarity	NPC228184
0.5273	Remote Similarity	NPC99597
0.5273	Remote Similarity	NPC482119
0.5273	Remote Similarity	NPC482120
0.5273	Remote Similarity	NPC110776
0.5179	Remote Similarity	NPC476153
0.5167	Remote Similarity	NPC109183
0.5091	Remote Similarity	NPC20354
0.5088	Remote Similarity	NPC48208
0.5088	Remote Similarity	NPC271590
0.5088	Remote Similarity	NPC601395
0.5082	Remote Similarity	NPC175504
0.5082	Remote Similarity	NPC3642

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC482487 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3624
0.1-0.2	5307
0.2-0.3	207
0.3-0.4	7
0.4-0.5	4
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
0.5472	Remote Similarity	NPD1550	Phase 2

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