NPASS Compound

Natural Product: NPC11226

Natural Product ID	NPC11226
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	CIQAFMGHGPCUFZ-SOTFOKLTSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	101010556
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0002585] O-methylated flavonoids [CHEMONTID:0002596] 4'-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 72 76 0 0 0 0 0 0 0 0999 V2000 -2.9210 6.1563 0.0528 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9266 4.7092 0.5402 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3420 4.1509 0.4534 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3414 2.6712 0.4758 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3317 2.0818 0.8392 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1495 1.8677 0.0622 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9495 2.6892 0.4525 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6925 2.0132 0.1304 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1217 2.1335 -1.1115 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0676 1.5107 -1.4205 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7212 0.7436 -0.4819 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1694 0.6061 0.7739 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8303 -0.1603 1.6994 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3830 -0.3223 2.8483 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0370 -0.7617 1.3069 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5415 -0.5934 0.0488 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7758 -1.1965 -0.3838 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5692 -1.9969 0.3935 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7538 -2.5612 -0.0563 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1798 -2.3254 -1.3378 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4143 -1.5276 -2.1533 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2426 -0.9787 -1.6844 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8454 -1.2814 -3.4703 O 0 0 0 0 0 0 0 0 0 0 0 0 8.3408 -2.8594 -1.8271 O 0 0 0 0 0 0 0 0 0 0 0 0 9.1252 -3.6800 -0.9846 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8602 0.1513 -0.7870 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0326 1.2433 1.0658 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5721 1.1026 2.3140 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7762 2.9044 -2.0578 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0497 3.9341 -0.1941 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0861 0.6468 0.6658 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0740 -0.4199 -0.2276 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9009 -1.3287 -0.1193 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3785 -2.7428 -0.4947 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.3261 -3.2436 0.5756 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.0264 -2.0146 1.1428 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.3706 -2.3547 1.7429 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2220 -1.1600 0.0607 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6841 -3.9362 1.5831 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1592 -2.5771 -1.6533 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9153 -1.0427 -1.0853 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1297 4.5966 1.5106 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9534 6.4100 -0.3277 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7109 6.8572 0.8849 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2045 6.2995 -0.7562 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6411 4.7205 1.5912 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7766 4.5682 -0.4722 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1316 1.7532 -1.0524 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0172 2.9356 1.5492 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4924 1.6230 -2.4056 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5789 -1.3693 2.0138 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2600 -2.2049 1.4182 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3358 -3.1775 0.5903 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6348 -0.3510 -2.3200 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8215 -1.4299 -3.6946 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0321 -4.0039 -1.5582 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5174 -3.0313 -0.1687 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5588 -4.5319 -0.5925 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8800 0.1938 2.6256 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4279 2.4457 -2.6839 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1230 -0.0438 -1.2495 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3870 -1.3199 0.8486 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5254 -3.4194 -0.6702 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1225 -3.8925 0.1433 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4195 -1.5451 1.9413 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1956 -1.7623 1.2763 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3756 -2.2035 2.8477 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5986 -3.4283 1.5782 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2964 -4.6414 1.9076 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5907 -2.4413 -2.4543 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3466 -1.8279 -1.2640 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8856 3.9710 1.6027 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 4 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 2 0 13 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 21 23 1 0 20 24 1 0 24 25 1 0 16 26 1 0 12 27 2 0 27 28 1 0 9 29 1 0 7 30 1 0 6 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 36 38 1 0 35 39 1 0 34 40 1 0 33 41 1 0 3 42 1 0 30 2 1 0 38 32 1 0 27 8 1 0 26 11 1 0 22 17 1 0 1 43 1 0 1 44 1 0 1 45 1 0 2 46 1 1 3 47 1 6 6 48 1 6 7 49 1 1 10 50 1 0 15 51 1 0 18 52 1 0 19 53 1 0 22 54 1 0 23 55 1 0 25 56 1 0 25 57 1 0 25 58 1 0 28 59 1 0 29 60 1 0 32 61 1 6 33 62 1 1 34 63 1 6 35 64 1 6 36 65 1 1 37 66 1 0 37 67 1 0 37 68 1 0 39 69 1 0 40 70 1 0 41 71 1 0 42 72 1 0 M END

Standard InCHIKey	CIQAFMGHGPCUFZ-SOTFOKLTSA-N
Standard InCHI	InChI=1S/C28H30O14/c1-9-21(33)24(36)27(42-28-25(37)23(35)20(32)10(2)40-28)26(39-9)19-14(31)8-17-18(22(19)34)13(30)7-16(41-17)11-4-5-15(38-3)12(29)6-11/h4-10,20-21,23,25-29,31-35,37H,1-3H3/t9-,10-,20-,21-,23+,25+,26+,27-,28-/m0/s1
SMILES	C[C@H]1[C@@H](C(=O)[C@@H]([C@@H](c2c(cc3c(c(=O)cc(c4ccc(c(c4)O)OC)o3)c2O)O)O1)O[C@H]1[C@@H]([C@@H]([C@H]([C@H](C)O1)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	590.16	Volume:	549.397 ? Van der Waals volume.
Dense:	1.074	LogP:	0.573 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.107 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.354 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	31.0
TPSA:	225.81 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	7.0	Rings:	5.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.211	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.943	Fsp³:	0.429
MCE-18:	120.75 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.641	Fluc inhibitor:	0.133 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.772 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.63 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.162	Promiscuous compounds:	0.39

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.228	MDCK Permeability:	-5.429
Pgp-inhibitor:	0.009	Pgp-substrate:	0.976
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):	0.054
20% Bioavailability (F20%):	0.317	30% Bioavailability (F30%):	0.912
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.64
Plasma Protein Binding (PPB):	85.58%	Volume Distribution (VD):	-0.126
Fu:	11.231% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.99
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.511
BSEP inhibitor:	0.065

ADMET: Metabolism

CYP1A2-inhibitor:	0.002	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.072	CYP2C9-substrate:	0.004
CYP2D6-inhibitor:	0.006	CYP2D6-substrate:	0.1
CYP3A4-inhibitor:	0.009	CYP3A4-substrate:	0.655
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.494 ? 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):

1.41

Half-life (T1/2):

3.627

ADMET: Toxicity

hERG Blockers:	0.012	hERG Blockers (10um):	0.192
Human Hepatotoxicity (H-HT):	0.449	Drug-induced Liver Injury (DILI):	0.857
AMES Toxicity:	0.832	Rat Oral Acute Toxicity:	0.152
Maximum Recommended Daily Dose:	0.305	Skin Sensitization:	0.977
Carcinogencity:	0.137	Eye Corrosion:	0.0
Eye Irritation:	0.645	Respiratory Toxicity:	0.078
Drug-induced Neurotoxicity:	0.002	Ototoxicity:	0.743
Hematotoxicity:	0.175	Drug-induced Nephrotoxicity:	0.228
Genotoxicity:	0.923	RPMI-8226 Immunitoxicity:	0.357
A549 Cytotoxicity:	0.754	Hek293 Cytotoxicity:	0.607
BCF:	0.477 ? 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:	3.149 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.662 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.95 ? 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
NPO30179	Cassia occidentalis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21080643]
NPO30179	Cassia occidentalis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30179	Cassia occidentalis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30179	Cassia occidentalis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

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 NPC11226 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	13111
0.1-0.2	32349
0.2-0.3	3570
0.3-0.4	687
0.4-0.5	126
0.5-0.6	9
0.6-0.7	3
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8171	Intermediate Similarity	NPC294629
0.8171	Intermediate Similarity	NPC131407
0.6522	Remote Similarity	NPC78734
0.6237	Remote Similarity	NPC605855
0.6061	Remote Similarity	NPC256760
0.5714	Remote Similarity	NPC257566
0.5545	Remote Similarity	NPC209296
0.5253	Remote Similarity	NPC603300
0.52	Remote Similarity	NPC604854
0.5155	Remote Similarity	NPC111249
0.5149	Remote Similarity	NPC218488
0.5133	Remote Similarity	NPC198199
0.5052	Remote Similarity	NPC22832
0.505	Remote Similarity	NPC47923

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC11226 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3587
0.1-0.2	5459
0.2-0.3	93
0.3-0.4	9
0.4-0.5	0
0.5-0.6	2
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
0.5545	Remote Similarity	NPD7054	Phase 4
0.5093	Remote Similarity	NPD7472	Pre-clinical

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