NPASS Compound

Natural Product: NPC211445

Natural Product ID	NPC211445
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KLQXMRBGMLHBBQ-RMKNXTFCSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	14413436
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0000198] Oligosaccharides

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 2D 103107 0 0 0 0 0 0 0 0999 V2000 -4.7181 0.3349 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3086 0.8479 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0481 -0.6293 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6386 -1.1424 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4895 -0.1782 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1595 1.8121 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4895 2.7762 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9200 3.2893 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1700 4.5883 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9200 5.8874 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4895 6.4004 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 7.8776 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0105 9.3548 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2709 10.8320 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1219 11.7962 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3824 13.2734 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7919 13.7864 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9410 12.8223 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6805 11.3451 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3505 13.3353 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0524 15.2637 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4619 15.7767 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4200 5.8874 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1700 4.5883 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3191 5.5525 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4681 6.5167 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2077 7.9939 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7077 7.9939 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4577 9.2929 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7077 10.5920 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2077 10.5920 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4577 9.2929 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.1172 11.1050 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.6067 8.3287 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4472 6.5167 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4200 3.2893 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8296 2.7762 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0900 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9410 0.3349 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4996 0.7860 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7600 -0.6912 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1696 -1.2042 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3186 -0.2401 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7282 -0.7531 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.9887 -2.2303 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8396 -3.1945 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4300 -2.6814 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1001 -4.6717 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9510 -5.6359 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.3982 -2.7433 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9791 3.6241 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9200 0.3349 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4895 -2.1065 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3086 -2.1065 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2312 1.7444 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5388 -0.4419 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1277 -0.1782 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0586 2.1469 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8394 -0.7265 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3886 -2.4414 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4132 -1.3761 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 1.2990 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5302 1.9190 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9791 5.5525 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3586 7.3218 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2272 7.6171 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6844 8.3162 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4667 9.6153 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4877 9.0943 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2877 11.2832 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7667 14.2376 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8296 10.3809 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4996 12.3711 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9489 17.1862 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9749 14.3671 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8714 16.2897 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3191 3.6241 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2220 6.5755 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2833 4.4034 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7461 7.6565 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1172 7.4809 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6067 10.2571 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4472 12.0692 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7981 11.1050 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4681 12.0692 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3777 12.5822 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0163 8.8418 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5963 5.5525 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1595 1.8121 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6486 1.7502 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6110 -1.6554 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0582 1.2372 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 10.8772 0.2111 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2810 -3.6456 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9152 -6.7849 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9868 -4.4868 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8019 -6.6001 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 11.6587 -4.2205 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3886 4.1372 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5302 1.7051 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9720 -1.7691 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7181 -2.6196 0.0000 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 1 0 5 6 1 0 6 7 1 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 19 21 1 0 18 22 1 0 22 23 1 0 11 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 32 33 1 0 31 34 1 0 30 35 1 0 29 36 1 0 25 37 1 0 37 38 1 0 38 39 1 0 39 40 2 0 39 41 1 0 41 42 2 0 42 43 1 0 43 44 2 0 44 45 1 0 45 46 2 0 46 47 1 0 47 48 2 0 47 49 1 0 49 50 1 0 46 51 1 0 10 52 1 0 5 53 1 0 4 54 1 0 3 55 1 0 7 2 1 0 37 9 1 0 48 43 1 0 20 15 1 0 33 28 1 0 1 56 1 0 1 57 1 0 1 58 1 0 2 59 1 0 3 60 1 0 4 61 1 0 5 62 1 0 6 63 1 0 9 64 1 0 10 65 1 0 11 66 1 0 13 67 1 0 13 68 1 0 14 69 1 0 14 70 1 0 16 71 1 0 17 72 1 0 20 73 1 0 21 74 1 0 23 75 1 0 23 76 1 0 23 77 1 0 25 78 1 0 26 79 1 0 26 80 1 0 28 81 1 0 29 82 1 0 30 83 1 0 31 84 1 0 32 85 1 0 32 86 1 0 34 87 1 0 35 88 1 0 36 89 1 0 37 90 1 0 41 91 1 0 42 92 1 0 44 93 1 0 45 94 1 0 48 95 1 0 50 96 1 0 50 97 1 0 50 98 1 0 51 99 1 0 52100 1 0 53101 1 0 54102 1 0 55103 1 0 M END

Standard InCHIKey	KLQXMRBGMLHBBQ-RMKNXTFCSA-N
Standard InCHI	InChI=1S/C36H48O19/c1-16-26(41)28(43)30(45)36(52-16)55-33-31(46)35(49-11-10-18-5-8-22(47-2)20(38)12-18)53-24(15-51-34-29(44)27(42)21(39)14-50-34)32(33)54-25(40)9-6-17-4-7-19(37)23(13-17)48-3/h4-9,12-13,16,21,24,26-39,41-46H,10-11,14-15H2,1-3H3/b9-6+
SMILES	CC1C(C(C(C(O1)OC1C(C(OCCc2ccc(c(c2)O)OC)OC(COC2C(C(C(CO2)O)O)O)C1OC(=O)/C=C/c1ccc(c(c1)OC)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	784.28	Volume:	734.352 ? Van der Waals volume.
Dense:	1.068	LogP:	-0.775 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.035 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.25 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	15.0	Rigid Bonds:	32.0
TPSA:	282.21 ? Topological Polar Surface Area.	H-Bond Acceptor:	19.0
H-Bond Donor:	9.0	Rings:	5.0
Heavy Atoms:	19.0

MedChem Properties

QED Drug-Likeness Score:	0.074	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.288	Fsp³:	0.583
MCE-18:	126.947 ? 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:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.328	Fluc inhibitor:	0.545 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.258 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.81 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.27	Promiscuous compounds:	0.335

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.17	MDCK Permeability:	-5.291
Pgp-inhibitor:	0.0	Pgp-substrate:	0.999
PAMPA:	1.0 ? 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):	1.0
20% Bioavailability (F20%):	0.996	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.748
Plasma Protein Binding (PPB):	58.007%	Volume Distribution (VD):	-0.493
Fu:	35.729% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.005
OATP1B3 inhibitor:	0.984	BCRP inhibitor:	0.323
BSEP inhibitor:	0.026

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.995	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.923	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.112	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.996
HLM stability:	0.229 ? 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):

1.045

Half-life (T1/2):

3.59

ADMET: Toxicity

hERG Blockers:	0.086	hERG Blockers (10um):	0.684
Human Hepatotoxicity (H-HT):	0.337	Drug-induced Liver Injury (DILI):	0.512
AMES Toxicity:	0.846	Rat Oral Acute Toxicity:	0.127
Maximum Recommended Daily Dose:	0.309	Skin Sensitization:	0.339
Carcinogencity:	0.023	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.005
Drug-induced Neurotoxicity:	0.434	Ototoxicity:	0.993
Hematotoxicity:	0.015	Drug-induced Nephrotoxicity:	0.195
Genotoxicity:	0.042	RPMI-8226 Immunitoxicity:	0.195
A549 Cytotoxicity:	0.168	Hek293 Cytotoxicity:	0.887
BCF:	0.626 ? 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:	3.242 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.275 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.138 ? 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
NPO4802	Scrophularia ningpoensis	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1007/s11738-014-1619-4]
NPO4802	Scrophularia ningpoensis	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.5897/JMPR09.338]
NPO6541	Scrophularia buergeriana	Species	Scrophulariaceae	Eukaryota	roots	n.a.	n.a.	PMID[12444706]
NPO4802	Scrophularia ningpoensis	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6541	Scrophularia buergeriana	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4802	Scrophularia ningpoensis	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6541	Scrophularia buergeriana	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4802	Scrophularia ningpoensis	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6541	Scrophularia buergeriana	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6541	Scrophularia buergeriana	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4802	Scrophularia ningpoensis	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4802	Scrophularia ningpoensis	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO6541	Scrophularia buergeriana	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO6541	Scrophularia buergeriana	Species	Scrophulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4802	Scrophularia ningpoensis	Species	Scrophulariaceae	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 NPC211445 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	14442
0.1-0.2	30389
0.2-0.3	4411
0.3-0.4	507
0.4-0.5	60
0.5-0.6	22
0.6-0.7	13
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9205	High Similarity	NPC259347
0.871	High Similarity	NPC470933
0.8039	Intermediate Similarity	NPC470927
0.7957	Intermediate Similarity	NPC34927
0.7742	Intermediate Similarity	NPC205864
0.7742	Intermediate Similarity	NPC247032
0.7677	Intermediate Similarity	NPC470934
0.7358	Intermediate Similarity	NPC257970
0.7216	Intermediate Similarity	NPC100998
0.7184	Intermediate Similarity	NPC473427
0.7083	Intermediate Similarity	NPC34587
0.7021	Intermediate Similarity	NPC76406
0.701	Intermediate Similarity	NPC252292
0.6939	Remote Similarity	NPC600370
0.6822	Remote Similarity	NPC476386
0.6762	Remote Similarity	NPC306890
0.6667	Remote Similarity	NPC298257
0.6667	Remote Similarity	NPC175214
0.6598	Remote Similarity	NPC611289
0.6569	Remote Similarity	NPC300894
0.6569	Remote Similarity	NPC23845
0.6542	Remote Similarity	NPC94871
0.6415	Remote Similarity	NPC471062
0.6204	Remote Similarity	NPC64195
0.6132	Remote Similarity	NPC106818
0.6055	Remote Similarity	NPC87403
0.596	Remote Similarity	NPC472350
0.596	Remote Similarity	NPC197316
0.596	Remote Similarity	NPC89105
0.5918	Remote Similarity	NPC46137
0.5909	Remote Similarity	NPC476398
0.5893	Remote Similarity	NPC229505
0.5888	Remote Similarity	NPC476382
0.5727	Remote Similarity	NPC476380
0.5688	Remote Similarity	NPC476384
0.5657	Remote Similarity	NPC260425
0.5657	Remote Similarity	NPC81515
0.5619	Remote Similarity	NPC269141
0.5586	Remote Similarity	NPC476381
0.5577	Remote Similarity	NPC263829
0.5565	Remote Similarity	NPC188393
0.5514	Remote Similarity	NPC112
0.5514	Remote Similarity	NPC119537
0.5413	Remote Similarity	NPC96795
0.5413	Remote Similarity	NPC264632
0.5258	Remote Similarity	NPC35731
0.5096	Remote Similarity	NPC64141
0.5049	Remote Similarity	NPC235294

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC211445 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4622
0.1-0.2	4417
0.2-0.3	106
0.3-0.4	4
0.4-0.5	0
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
0.596	Remote Similarity	NPD7266	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