NPASS Compound

Natural Product: NPC221398

Natural Product ID	NPC221398
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PJHJORWYAZKNAL-MFYRMPRMSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	51136406
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0000507] Isoflavonoid O-glycosides

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 70 74 0 0 0 0 0 0 0 0999 V2000 12.1847 -1.0819 -0.2497 C 0 0 0 0 0 0 0 0 0 0 0 0 11.1302 -1.9904 -0.1741 O 0 0 0 0 0 0 0 0 0 0 0 0 9.7844 -1.5916 -0.1239 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7656 -2.5162 -0.0496 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4467 -2.1132 -0.0008 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0856 -0.7808 -0.0237 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1141 0.1420 -0.0984 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4331 -0.2588 -0.1472 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6853 -0.3817 0.0289 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2857 0.6442 0.8570 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0423 1.0403 0.9402 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0606 0.4992 0.2443 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7585 0.9540 0.3671 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7362 0.3954 -0.3532 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0672 -0.6625 -1.2249 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3611 -1.1111 -1.3439 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3872 -0.5345 -0.6068 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6875 -0.9749 -0.7170 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9820 -1.9122 -1.4890 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5737 0.7764 -0.2980 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1623 1.7859 0.4725 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6993 2.8913 -0.4048 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1114 2.7181 -0.8416 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9366 2.2709 0.3171 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3276 1.0188 0.9277 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3543 -0.1423 -0.0075 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5833 -0.4994 -0.4959 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5159 -0.8943 0.4308 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.7706 -0.0771 0.2428 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.8542 -1.1195 0.1168 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.1025 -1.4199 -1.3321 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0068 -2.4589 -1.4786 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.2004 -2.3286 0.7511 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8993 -2.2297 0.2617 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.0149 -0.7484 0.7901 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0014 0.7581 1.3510 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0631 1.3113 1.4047 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8062 3.2682 1.3120 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2675 1.9479 -1.9848 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5749 4.1198 0.2210 O 0 0 0 0 0 0 0 0 0 0 0 0 12.2683 -0.5823 0.7417 H 0 0 0 0 0 0 0 0 0 0 0 0 13.1132 -1.6444 -0.4739 H 0 0 0 0 0 0 0 0 0 0 0 0 11.9484 -0.3312 -1.0322 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0150 -3.5693 -0.0300 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6292 -2.8409 0.0582 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8279 1.1849 -0.1161 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2419 0.4660 -0.2059 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0722 1.1237 1.4556 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5578 1.7578 1.0402 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2808 -1.1217 -1.8054 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6450 -1.9229 -2.0060 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3561 2.2676 1.0710 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0626 2.9150 -1.3232 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4885 3.7480 -1.1188 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9983 2.1794 0.1216 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9547 0.7723 1.8065 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6809 -0.0218 -0.8839 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9503 -1.0573 0.5187 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1224 -0.8544 1.4856 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7682 0.5131 -0.6798 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4884 -0.4868 -1.8347 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1494 -1.7101 -1.7967 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4875 -3.3008 -1.4952 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6634 -3.2484 0.3706 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2213 -2.2831 1.8595 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4774 -0.0901 0.2146 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3490 0.5244 2.0656 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2064 2.9796 2.1594 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4288 1.8166 -2.4838 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9180 4.1031 0.9563 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 2 0 6 7 1 0 7 8 2 0 6 9 1 0 9 10 2 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 2 0 17 18 1 0 18 19 2 0 14 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 30 33 1 0 33 34 1 0 30 35 1 1 29 36 1 0 25 37 1 0 24 38 1 0 23 39 1 0 22 40 1 0 8 3 1 0 18 9 1 0 37 21 1 0 17 12 1 0 34 28 1 0 1 41 1 0 1 42 1 0 1 43 1 0 4 44 1 0 5 45 1 0 7 46 1 0 8 47 1 0 10 48 1 0 13 49 1 0 15 50 1 0 16 51 1 0 21 52 1 1 22 53 1 6 23 54 1 6 24 55 1 6 25 56 1 1 26 57 1 0 26 58 1 0 28 59 1 1 29 60 1 6 31 61 1 0 31 62 1 0 32 63 1 0 33 64 1 0 33 65 1 0 35 66 1 0 36 67 1 0 38 68 1 0 39 69 1 0 40 70 1 0 M END

Standard InCHIKey	PJHJORWYAZKNAL-MFYRMPRMSA-N
Standard InCHI	InChI=1S/C27H30O13/c1-35-14-4-2-13(3-5-14)17-9-36-18-8-15(6-7-16(18)20(17)29)39-25-23(32)22(31)21(30)19(40-25)10-37-26-24(33)27(34,11-28)12-38-26/h2-9,19,21-26,28,30-34H,10-12H2,1H3/t19-,21-,22+,23-,24+,25-,26-,27-/m1/s1
SMILES	COc1ccc(cc1)c1coc2cc(ccc2c1=O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO[C@H]2[C@@H]([C@@](CO)(CO2)O)O)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	562.17	Volume:	525.947 ? Van der Waals volume.
Dense:	1.069	LogP:	1.295 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.806 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.875 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	29.0
TPSA:	197.74 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	6.0	Rings:	5.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.198	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.463	Fsp³:	0.444
MCE-18:	110.769 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.516	Fluc inhibitor:	0.317 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.861 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.214 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.066	Promiscuous compounds:	0.082

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.219	MDCK Permeability:	-5.184
Pgp-inhibitor:	0.0	Pgp-substrate:	0.3
PAMPA:	0.996 ? 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):	0.979
20% Bioavailability (F20%):	0.164	30% Bioavailability (F30%):	0.986
50% Bioavailability (F50%):	0.947

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.167
Plasma Protein Binding (PPB):	80.818%	Volume Distribution (VD):	-0.305
Fu:	19.965% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.113
BSEP inhibitor:	0.006

ADMET: Metabolism

CYP1A2-inhibitor:	0.004	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.035	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.911
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.0 ? 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):

1.863

Half-life (T1/2):

2.87

ADMET: Toxicity

hERG Blockers:	0.075	hERG Blockers (10um):	0.1
Human Hepatotoxicity (H-HT):	0.769	Drug-induced Liver Injury (DILI):	0.977
AMES Toxicity:	0.974	Rat Oral Acute Toxicity:	0.032
Maximum Recommended Daily Dose:	0.104	Skin Sensitization:	0.97
Carcinogencity:	0.497	Eye Corrosion:	0.0
Eye Irritation:	0.136	Respiratory Toxicity:	0.024
Drug-induced Neurotoxicity:	0.064	Ototoxicity:	0.947
Hematotoxicity:	0.256	Drug-induced Nephrotoxicity:	0.875
Genotoxicity:	0.849	RPMI-8226 Immunitoxicity:	0.208
A549 Cytotoxicity:	0.519	Hek293 Cytotoxicity:	0.517
BCF:	0.589 ? 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:	3.289 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.813 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.105 ? 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
NPO29215	Millettia nitida	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29215	Millettia nitida	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29215	Millettia nitida	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

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

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 NPC221398 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	19731
0.1-0.2	26901
0.2-0.3	2604
0.3-0.4	481
0.4-0.5	105
0.5-0.6	23
0.6-0.7	8
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8605	High Similarity	NPC235575
0.7073	Intermediate Similarity	NPC45165
0.7065	Intermediate Similarity	NPC51326
0.6737	Remote Similarity	NPC231194
0.6506	Remote Similarity	NPC25547
0.6395	Remote Similarity	NPC476442
0.6395	Remote Similarity	NPC215512
0.6354	Remote Similarity	NPC257714
0.6222	Remote Similarity	NPC43761
0.6105	Remote Similarity	NPC475155
0.6044	Remote Similarity	NPC229729
0.5955	Remote Similarity	NPC161749
0.5909	Remote Similarity	NPC135345
0.5843	Remote Similarity	NPC211014
0.5699	Remote Similarity	NPC601607
0.5612	Remote Similarity	NPC479405
0.5604	Remote Similarity	NPC603782
0.5556	Remote Similarity	NPC479404
0.5543	Remote Similarity	NPC73511
0.5455	Remote Similarity	NPC303913
0.5444	Remote Similarity	NPC487214
0.534	Remote Similarity	NPC600130
0.5294	Remote Similarity	NPC65711
0.5283	Remote Similarity	NPC475261
0.5269	Remote Similarity	NPC258035
0.5256	Remote Similarity	NPC182428
0.5238	Remote Similarity	NPC171533
0.5161	Remote Similarity	NPC478528
0.5122	Remote Similarity	NPC136095
0.51	Remote Similarity	NPC295613
0.51	Remote Similarity	NPC473657
0.5056	Remote Similarity	NPC227980
0.5054	Remote Similarity	NPC160515
0.5044	Remote Similarity	NPC473895

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC221398 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4770
0.1-0.2	4302
0.2-0.3	67
0.3-0.4	6
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
0.5955	Remote Similarity	NPD4381	Clinical (unspecified phase)

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