NPASS Compound

Natural Product: NPC223860

Natural Product ID	NPC223860
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Calabricoside B
IUPAC Name	[(2S,3R,4S,5R,6S)-6-[(2S,3R,4S,5S)-2-[2-(3,4-dihydroxyphenyl)-5-hydroxy-4-oxo-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-4,5-dihydroxy-2-methyloxan-3-yl] (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Synonyms	calabricoside B
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL444123
PubChem CID	11072999
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides [CHEMONTID:0003533] Flavonoid-7-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 108114 0 0 0 0 0 0 0 0999 V2000 -12.5175 2.1952 1.9852 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.5600 1.2161 2.2626 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.7371 1.0162 1.0005 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.7706 0.0446 1.2263 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.9412 0.0184 0.0815 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.7510 -0.6363 0.3098 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5067 -0.0907 0.0983 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2709 1.1759 -0.3821 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9885 1.6709 -0.5744 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7674 2.9365 -1.0539 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9150 0.8567 -0.2703 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1338 -0.4345 0.2195 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4277 -0.8768 0.3917 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1072 -1.1456 0.4848 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8157 -0.8115 0.3536 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5474 0.4333 -0.1157 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6265 1.2916 -0.4379 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4001 2.4419 -0.8737 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2636 0.9690 -0.3111 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2951 1.7037 0.7607 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.3638 2.9840 0.8090 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3520 3.8883 1.5511 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1157 3.2743 2.7070 C 0 0 1 0 0 0 0 0 0 0 0 0 2.1685 2.3570 2.1339 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7306 2.0030 0.7153 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5767 1.1013 0.1232 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2339 1.5871 -0.9802 C 0 0 2 0 0 0 0 0 0 0 0 0 2.9742 0.7427 -2.0678 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8806 -0.3401 -2.1007 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3076 -1.3827 -3.0369 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2067 0.1404 -2.6841 C 0 0 1 0 0 0 0 0 0 0 0 0 5.2665 1.6284 -2.3015 C 0 0 2 0 0 0 0 0 0 0 0 0 4.7349 1.6586 -0.8568 C 0 0 1 0 0 0 0 0 0 0 0 0 5.1884 2.8765 -0.3424 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3191 2.2660 -3.0918 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2951 -0.4564 -1.9925 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2654 -1.1043 -2.7440 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2052 -1.1739 -3.9986 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4062 -1.7358 -2.0865 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5135 -1.6871 -0.7776 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5962 -2.2738 -0.0085 C 0 0 0 0 0 0 0 0 0 0 0 0 10.6432 -2.9543 -0.5713 C 0 0 0 0 0 0 0 0 0 0 0 0 11.6684 -3.5036 0.2063 C 0 0 0 0 0 0 0 0 0 0 0 0 11.6585 -3.3772 1.5745 C 0 0 0 0 0 0 0 0 0 0 0 0 10.6038 -2.6909 2.1499 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6092 -2.1601 1.3726 C 0 0 0 0 0 0 0 0 0 0 0 0 10.6127 -2.5733 3.5446 O 0 0 0 0 0 0 0 0 0 0 0 0 12.6811 -3.9247 2.3571 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4296 2.8978 2.1741 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8157 4.2793 3.4103 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8144 -1.7883 0.7198 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2235 -2.9059 1.4192 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3381 -3.9095 1.7755 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9882 -3.8092 1.4327 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4141 -2.7053 0.7363 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4945 -1.7113 0.3919 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7516 -2.6126 0.3944 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8982 -4.8226 1.7894 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.7962 -0.7042 -0.9750 C 0 0 1 0 0 0 0 0 0 0 0 0 -10.8834 0.2945 -1.3502 C 0 0 2 0 0 0 0 0 0 0 0 0 -11.6537 0.7258 -0.1452 C 0 0 2 0 0 0 0 0 0 0 0 0 -12.2745 1.9548 -0.4740 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.7001 -0.1584 -2.3687 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.0475 -1.0212 -2.0934 O 0 0 0 0 0 0 0 0 0 0 0 0 -12.0394 3.0612 1.9009 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.9396 1.5779 3.0960 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.1129 0.2865 2.5090 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1737 1.9628 0.7799 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8716 1.0637 -0.2518 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0868 1.8293 -0.6274 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4929 3.1875 -1.9789 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5797 -1.8691 0.7685 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0219 1.2465 1.7084 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9853 4.5858 0.9685 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4094 4.5665 2.0448 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4496 2.7917 3.4369 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1049 1.4000 2.7140 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8553 2.9585 0.1245 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9161 2.6454 -1.2057 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9994 -0.6879 -1.0704 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0518 -2.1583 -3.2512 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3730 -1.7882 -2.6429 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1215 -0.8487 -4.0043 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2902 -0.0079 -3.7647 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2708 2.0425 -2.3475 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1903 0.7844 -0.3554 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0385 2.6678 0.1461 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3031 1.8261 -3.9770 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1676 -2.2465 -2.6540 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7049 -1.1531 -0.2492 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6910 -3.0781 -1.6554 H 0 0 0 0 0 0 0 0 0 0 0 0 12.5018 -4.0469 -0.2587 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7858 -1.6254 1.8182 H 0 0 0 0 0 0 0 0 0 0 0 0 10.4087 -1.6431 3.9388 H 0 0 0 0 0 0 0 0 0 0 0 0 13.3559 -3.3531 2.8535 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8021 2.9816 3.0765 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3199 4.8733 2.8148 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2753 -3.0116 1.7054 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6613 -4.7795 2.3215 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8825 -0.9076 -0.1665 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4547 -3.2562 0.6625 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5993 -5.7883 1.9011 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2254 -1.6346 -0.5330 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3284 1.2026 -1.7277 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.4756 0.0289 0.1354 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.5082 2.5304 -0.7840 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.9684 0.6051 -2.9736 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2111 -1.9693 -2.3390 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 7 8 2 0 8 9 1 0 9 10 1 0 9 11 2 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 16 19 1 0 19 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 29 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 32 35 1 0 31 36 1 0 36 37 1 0 37 38 2 0 37 39 1 0 39 40 2 0 40 41 1 0 41 42 2 0 42 43 1 0 43 44 2 0 44 45 1 0 45 46 2 0 45 47 1 0 44 48 1 0 24 49 1 0 23 50 1 0 15 51 1 0 51 52 2 0 52 53 1 0 53 54 2 0 54 55 1 0 55 56 2 0 55 57 1 0 54 58 1 0 5 59 1 0 59 60 1 0 60 61 1 0 61 62 1 0 60 63 1 0 59 64 1 0 61 3 1 0 13 7 1 0 25 20 1 0 33 27 1 0 46 41 1 0 56 51 1 0 17 11 1 0 1 65 1 0 2 66 1 0 2 67 1 0 3 68 1 6 5 69 1 6 8 70 1 0 10 71 1 0 13 72 1 0 20 73 1 1 22 74 1 0 22 75 1 0 23 76 1 1 24 77 1 1 25 78 1 6 27 79 1 6 29 80 1 1 30 81 1 0 30 82 1 0 30 83 1 0 31 84 1 6 32 85 1 1 33 86 1 1 34 87 1 0 35 88 1 0 39 89 1 0 40 90 1 0 42 91 1 0 43 92 1 0 46 93 1 0 47 94 1 0 48 95 1 0 49 96 1 0 50 97 1 0 52 98 1 0 53 99 1 0 56100 1 0 57101 1 0 58102 1 0 59103 1 1 60104 1 6 61105 1 1 62106 1 0 63107 1 0 64108 1 0 M END

Standard InCHIKey	BHZKXYVGAILXRA-DUXRVPMWSA-N
Standard InCHI	InChI=1S/C41H44O23/c1-14-35(62-26(49)7-3-15-2-5-18(43)20(45)8-15)32(54)34(56)39(58-14)64-38-28(50)23(48)13-57-41(38)63-37-30(52)27-22(47)10-17(59-40-33(55)31(53)29(51)25(12-42)61-40)11-24(27)60-36(37)16-4-6-19(44)21(46)9-16/h2-11,14,23,25,28-29,31-35,38-48,50-51,53-56H,12-13H2,1H3/b7-3+/t14-,23-,25+,28-,29+,31-,32-,33+,34+,35-,38+,39-,40+,41-/m0/s1
SMILES	OC[C@H]1O[C@@H](Oc2cc(O)c3c(c2)oc(c(c3=O)O[C@@H]2OC[C@@H]([C@@H]([C@H]2O[C@@H]2O[C@@H](C)[C@@H]([C@H]([C@H]2O)O)OC(=O)/C=C/c2ccc(c(c2)O)O)O)O)c2ccc(c(c2)O)O)[C@@H]([C@H]([C@@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	904.23	Volume:	825.698 ? Van der Waals volume.
Dense:	1.095	LogP:	0.819 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.15 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.997 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	44.0
TPSA:	374.88 ? Topological Polar Surface Area.	H-Bond Acceptor:	23.0
H-Bond Donor:	13.0	Rings:	7.0
Heavy Atoms:	23.0

MedChem Properties

QED Drug-Likeness Score:	0.044	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.725	Fsp³:	0.415
MCE-18:	172.345 ? 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:	1
Colloidal aggregators:	0.701	Fluc inhibitor:	0.571 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.897 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.666 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.309	Promiscuous compounds:	0.603

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.697	MDCK Permeability:	-5.042
Pgp-inhibitor:	0.0	Pgp-substrate:	0.137
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):	0.999
20% Bioavailability (F20%):	0.999	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.002
Plasma Protein Binding (PPB):	74.449%	Volume Distribution (VD):	-0.167
Fu:	23.454% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.042
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.254
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.996
HLM stability:	0.018 ? 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):

1.315

Half-life (T1/2):

6.609

ADMET: Toxicity

hERG Blockers:	0.005	hERG Blockers (10um):	0.106
Human Hepatotoxicity (H-HT):	0.727	Drug-induced Liver Injury (DILI):	0.998
AMES Toxicity:	0.987	Rat Oral Acute Toxicity:	0.004
Maximum Recommended Daily Dose:	0.009	Skin Sensitization:	1.0
Carcinogencity:	0.024	Eye Corrosion:	0.0
Eye Irritation:	0.021	Respiratory Toxicity:	0.001
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.998
Hematotoxicity:	0.056	Drug-induced Nephrotoxicity:	0.798
Genotoxicity:	0.995	RPMI-8226 Immunitoxicity:	0.066
A549 Cytotoxicity:	0.997	Hek293 Cytotoxicity:	0.707
BCF:	0.602 ? 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:	3.354 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.182 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.436 ? 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
NPO30903	Putoria calabrica	n.a.	n.a.	n.a.	n.a.	aerial part	n.a.	PMID[11473436]
NPO30903	Putoria calabrica	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[11473436]
NPO30903	Putoria calabrica	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]

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
Non-molecular	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
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	300.0	nM	PMID[11473436]

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 NPC223860 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	18714
0.1-0.2	27190
0.2-0.3	3039
0.3-0.4	565
0.4-0.5	286
0.5-0.6	44
0.6-0.7	10
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
0.7273	Intermediate Similarity	NPC14187
0.6581	Remote Similarity	NPC164704
0.6441	Remote Similarity	NPC470715
0.626	Remote Similarity	NPC470719
0.626	Remote Similarity	NPC470717
0.623	Remote Similarity	NPC295625
0.6198	Remote Similarity	NPC470716
0.6167	Remote Similarity	NPC480441
0.608	Remote Similarity	NPC470720
0.6038	Remote Similarity	NPC136042
0.6017	Remote Similarity	NPC484301
0.597	Remote Similarity	NPC97817
0.5909	Remote Similarity	NPC605784
0.5833	Remote Similarity	NPC84362
0.5789	Remote Similarity	NPC30011
0.5776	Remote Similarity	NPC64425
0.5678	Remote Similarity	NPC35119
0.5672	Remote Similarity	NPC72554
0.5645	Remote Similarity	NPC25523
0.5546	Remote Similarity	NPC32641
0.5546	Remote Similarity	NPC256188
0.552	Remote Similarity	NPC470712
0.5505	Remote Similarity	NPC289667
0.5478	Remote Similarity	NPC251417
0.5455	Remote Similarity	NPC297987
0.5447	Remote Similarity	NPC81042
0.5433	Remote Similarity	NPC470718
0.5407	Remote Similarity	NPC231787
0.5385	Remote Similarity	NPC470405
0.5385	Remote Similarity	NPC33083
0.5362	Remote Similarity	NPC249560
0.5351	Remote Similarity	NPC116458
0.5351	Remote Similarity	NPC246943
0.5344	Remote Similarity	NPC488078
0.5308	Remote Similarity	NPC470713
0.5289	Remote Similarity	NPC104883
0.5289	Remote Similarity	NPC488679
0.5267	Remote Similarity	NPC156785
0.5259	Remote Similarity	NPC21359
0.5259	Remote Similarity	NPC460984
0.5208	Remote Similarity	NPC482520
0.5208	Remote Similarity	NPC482519
0.5133	Remote Similarity	NPC271692
0.5126	Remote Similarity	NPC471748
0.5124	Remote Similarity	NPC240306
0.5103	Remote Similarity	NPC482521
0.5079	Remote Similarity	NPC214621
0.5079	Remote Similarity	NPC34267
0.5072	Remote Similarity	NPC275977
0.5044	Remote Similarity	NPC277205
0.5044	Remote Similarity	NPC37919
0.5044	Remote Similarity	NPC189142
0.5044	Remote Similarity	NPC77660
0.5043	Remote Similarity	NPC276377
0.5038	Remote Similarity	NPC162394

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC223860 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4771
0.1-0.2	4326
0.2-0.3	45
0.3-0.4	3
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
0.5081	Remote Similarity	NPD7251	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