NPASS Compound

Natural Product: NPC535419

Natural Product ID	NPC535419
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Cogoxin
IUPAC Name	3-[(3~{R},5~{S},8~{R},9~{R},10~{R},12~{S},13~{R},14~{R},17~{R})-3-[(2~{R},4~{S},5~{S},6~{S})-5-[(2~{S},4~{S},5~{S},6~{S})-5-[(2~{S},4~{S},5~{S},6~{S})-4,5-dihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-4-hydroxy-6-methyl-tetrahydropyran-2-yl]oxy-4-hydroxy-6-methyl-tetrahydropyran-2-yl]oxy-12,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-2~{H}-furan-5-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 119126 0 0 0 0 0 0 0 0999 V2000 12.4530 0.2528 1.3680 C 0 0 0 0 0 0 0 0 0 0 0 0 11.5201 0.8065 0.2976 C 0 0 2 0 0 0 0 0 0 0 0 0 10.2603 0.6064 0.6603 O 0 0 0 0 0 0 0 0 0 0 0 0 9.5186 -0.4036 0.2020 C 0 0 1 0 0 0 0 0 0 0 0 0 8.1777 -0.1087 -0.0314 O 0 0 0 0 0 0 0 0 0 0 0 0 7.2939 -0.8203 0.7272 C 0 0 2 0 0 0 0 0 0 0 0 0 6.2150 -1.5055 -0.0925 C 0 0 2 0 0 0 0 0 0 0 0 0 6.6796 -2.7749 -0.7320 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6291 -0.6531 -1.0105 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1059 0.4905 -0.5000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.8361 0.2198 -0.0081 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8255 0.9016 -0.6782 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0199 1.7788 0.2167 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4302 1.6552 1.6742 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6711 1.5920 0.1551 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2601 0.3191 0.5310 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0899 0.2123 0.3127 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8509 -0.0173 1.4416 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.6801 -1.2761 1.1276 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1295 -1.1106 -0.2818 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0164 0.0951 -0.5098 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9932 0.3151 -2.0101 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4665 1.3375 0.1237 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.4015 2.4688 0.2407 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7996 2.2597 -0.1944 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3631 0.8986 0.0189 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.3553 -0.2137 0.0657 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.9560 -1.4912 -0.5243 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4116 -1.5151 0.0178 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.7772 -2.8591 -0.1000 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.1947 -0.6156 -0.8524 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.2051 -1.2879 -2.2500 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5814 -0.2556 -0.4644 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.9405 -0.2340 0.9484 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.2993 0.8705 1.6234 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.5910 0.5397 3.0085 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.9605 1.3548 3.9229 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.3947 -0.7977 3.1375 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.0739 -1.3638 1.8848 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.7843 1.1391 -1.0763 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4646 1.7764 -0.8303 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4240 0.6698 -1.0451 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.9495 0.8332 -2.3185 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9008 1.0673 1.5179 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9950 -0.7528 -0.2325 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9328 -0.1705 -1.2592 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6470 -1.1989 -1.8691 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9796 1.1960 0.5024 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5100 0.2198 1.5495 C 0 0 2 0 0 0 0 0 0 0 0 0 7.2972 0.8355 2.4839 O 0 0 0 0 0 0 0 0 0 0 0 0 10.0239 -1.1221 -1.0185 C 0 0 0 0 0 0 0 0 0 0 0 0 11.5145 -1.1902 -1.0892 C 0 0 2 0 0 0 0 0 0 0 0 0 11.9745 -1.9080 0.0119 O 0 0 0 0 0 0 0 0 0 0 0 0 11.9810 0.2646 -1.0151 C 0 0 2 0 0 0 0 0 0 0 0 0 13.3687 0.3135 -1.0503 O 0 0 0 0 0 0 0 0 0 0 0 0 13.3733 -0.1728 0.9264 H 0 0 0 0 0 0 0 0 0 0 0 0 12.6449 1.0314 2.1265 H 0 0 0 0 0 0 0 0 0 0 0 0 11.8942 -0.5585 1.9162 H 0 0 0 0 0 0 0 0 0 0 0 0 11.7283 1.9173 0.2712 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4889 -1.1994 1.0098 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7176 -1.5384 1.4272 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4163 -1.7788 0.6360 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3743 -3.3205 -0.0700 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7739 -3.4410 -0.8354 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0664 -2.6388 -1.7582 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9435 1.2155 -1.3474 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2507 1.5511 -1.4954 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2188 2.8504 -0.0500 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5748 2.0148 2.2808 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2744 2.3403 1.9140 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6229 0.6072 1.9804 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4638 0.2031 1.6096 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2990 -0.0908 2.3743 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5011 -1.3771 1.8569 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9618 -2.1116 1.1607 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5904 -2.0015 -0.7071 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1963 -0.9349 -0.8966 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9073 0.1945 -2.3172 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2250 1.3604 -2.2949 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5294 -0.4365 -2.5880 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5567 1.6132 -0.4886 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4166 2.9187 1.2788 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0013 3.3275 -0.3812 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9846 2.5989 -1.2594 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4519 2.9880 0.3791 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9354 0.8764 0.9829 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1718 -0.4650 1.1340 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4838 -2.3907 -0.0752 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9166 -1.5443 -1.6047 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3253 -1.2625 1.0700 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5544 -3.3695 0.7297 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2198 -2.3975 -2.1276 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3786 -0.9383 -2.8656 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1646 -1.0048 -2.7099 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2770 -0.9152 -1.0615 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3848 1.8970 1.2713 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.9975 -1.9291 1.5068 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2582 -2.0716 1.9387 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9841 1.0395 -2.1836 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.6131 1.6912 -0.6697 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3520 2.5866 -1.6105 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3395 2.2818 0.1233 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6442 1.2111 -2.8826 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5628 1.9877 1.9733 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7438 0.6708 2.1214 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3282 -1.4651 -0.7586 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5811 -1.3440 0.4947 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3447 0.3222 -2.0788 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2788 -0.7765 -2.5190 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8696 1.6208 -0.0042 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4840 1.9967 1.0412 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6074 -0.2757 2.0034 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4268 1.7810 2.2184 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6410 -2.1759 -1.0703 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6539 -0.6342 -1.9443 H 0 0 0 0 0 0 0 0 0 0 0 0 11.8015 -1.6683 -2.0383 H 0 0 0 0 0 0 0 0 0 0 0 0 11.8560 -2.8702 -0.1833 H 0 0 0 0 0 0 0 0 0 0 0 0 11.5062 0.8193 -1.8293 H 0 0 0 0 0 0 0 0 0 0 0 0 13.6580 0.8997 -1.7782 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 1 0 7 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 13 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 6 21 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 6 31 33 1 0 33 34 1 0 34 35 2 0 35 36 1 0 36 37 2 0 36 38 1 0 38 39 1 0 33 40 1 0 40 41 1 0 41 42 1 0 42 43 1 6 23 44 1 0 16 45 1 0 45 46 1 0 46 47 1 0 10 48 1 0 48 49 1 0 49 50 1 0 4 51 1 0 51 52 1 0 52 53 1 0 52 54 1 0 54 55 1 0 54 2 1 0 49 6 1 0 46 12 1 0 44 18 1 0 27 21 1 0 42 31 1 0 42 26 1 0 39 34 1 0 1 56 1 0 1 57 1 0 1 58 1 0 2 59 1 6 4 60 1 1 6 61 1 1 7 62 1 1 8 63 1 0 8 64 1 0 8 65 1 0 10 66 1 6 12 67 1 6 13 68 1 6 14 69 1 0 14 70 1 0 14 71 1 0 16 72 1 1 18 73 1 1 19 74 1 0 19 75 1 0 20 76 1 0 20 77 1 0 22 78 1 0 22 79 1 0 22 80 1 0 23 81 1 6 24 82 1 0 24 83 1 0 25 84 1 0 25 85 1 0 26 86 1 1 27 87 1 1 28 88 1 0 28 89 1 0 29 90 1 1 30 91 1 0 32 92 1 0 32 93 1 0 32 94 1 0 33 95 1 6 35 96 1 0 39 97 1 0 39 98 1 0 40 99 1 0 40100 1 0 41101 1 0 41102 1 0 43103 1 0 44104 1 0 44105 1 0 45106 1 0 45107 1 0 46108 1 6 47109 1 0 48110 1 0 48111 1 0 49112 1 1 50113 1 0 51114 1 0 51115 1 0 52116 1 6 53117 1 0 54118 1 6 55119 1 0 M END

Standard InCHIKey	LTMHDMANZUZIPE-RNDPEBKUSA-N
Standard InCHI	InChI=1S/C41H64O14/c1-19-36(47)28(42)15-34(50-19)54-38-21(3)52-35(17-30(38)44)55-37-20(2)51-33(16-29(37)43)53-24-8-10-39(4)23(13-24)6-7-26-27(39)14-31(45)40(5)25(9-11-41(26,40)48)22-12-32(46)49-18-22/h12,19-21,23-31,33-38,42-45,47-48H,6-11,13-18H2,1-5H3/t19-,20-,21-,23-,24+,25+,26+,27+,28-,29-,30-,31-,33-,34-,35-,36+,37+,38+,39+,40+,41+/m0/s1
SMILES	C[C@@H]1O[C@@H](O[C@@H]2[C@H](C)O[C@@H](O[C@@H]3[C@H](C)O[C@@H](O[C@@H]4CC[C@]5(C)[C@@H](CC[C@@H]6[C@H]5C[C@H](O)[C@@]5(C)[C@@H](C7=CC(=O)OC7)CC[C@@]65O)C4)C[C@@H]3O)C[C@@H]2O)C[C@H](O)[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	780.43	Volume:	767.03 ? Van der Waals volume.
Dense:	1.017	LogP:	2.039 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.429 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.106 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	44.0
TPSA:	203.06 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	6.0	Rings:	8.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.162	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.122	Fsp³:	0.927
MCE-18:	150.278 ? 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:	0.763	Fluc inhibitor:	0.004 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.008 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.239	Promiscuous compounds:	0.738

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.842	MDCK Permeability:	-5.046
Pgp-inhibitor:	0.0	Pgp-substrate:	0.997
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):	0.003
20% Bioavailability (F20%):	0.339	30% Bioavailability (F30%):	0.116
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.972
Plasma Protein Binding (PPB):	45.054%	Volume Distribution (VD):	-0.576
Fu:	47.03% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.985
OATP1B3 inhibitor:	0.733	BCRP inhibitor:	0.01
BSEP inhibitor:	0.318

ADMET: Metabolism

CYP1A2-inhibitor:	0.674	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.24	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	0.798
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.005
HLM stability:	0.398 ? 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):

1.022

Half-life (T1/2):

3.677

ADMET: Toxicity

hERG Blockers:	0.149	hERG Blockers (10um):	0.59
Human Hepatotoxicity (H-HT):	0.86	Drug-induced Liver Injury (DILI):	0.92
AMES Toxicity:	0.967	Rat Oral Acute Toxicity:	1.0
Maximum Recommended Daily Dose:	1.0	Skin Sensitization:	1.0
Carcinogencity:	0.911	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	1.0
Drug-induced Neurotoxicity:	0.077	Ototoxicity:	0.983
Hematotoxicity:	0.996	Drug-induced Nephrotoxicity:	0.997
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.971
A549 Cytotoxicity:	1.0	Hek293 Cytotoxicity:	0.999
BCF:	0.75 ? 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:	3.341 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.819 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.06 ? 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
NPO22810	Streptomyces	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[11141106]
NPO22810	Streptomyces	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[11374972]
NPO22810	Streptomyces	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[15217282]
NPO22810	Streptomyces	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[15270566]
NPO22810	Streptomyces	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16149	Streptomyces purpurascens	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO53986	Streptomyces EUSA3B	Genus	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16149	Streptomyces purpurascens	Species	Streptomycetaceae	Bacteria	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 NPC535419 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	15685
0.1-0.2	29102
0.2-0.3	4717
0.3-0.4	153
0.4-0.5	100
0.5-0.6	74
0.6-0.7	14
0.7-0.8	1
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC173555
0.8395	Intermediate Similarity	NPC72260
0.8235	Intermediate Similarity	NPC208193
0.7634	Intermediate Similarity	NPC117445
0.7634	Intermediate Similarity	NPC308262
0.7619	Intermediate Similarity	NPC193893
0.7531	Intermediate Similarity	NPC471633
0.6897	Remote Similarity	NPC179412
0.6897	Remote Similarity	NPC471356
0.6897	Remote Similarity	NPC471353
0.6667	Remote Similarity	NPC55532
0.6465	Remote Similarity	NPC120390
0.6465	Remote Similarity	NPC74259
0.6429	Remote Similarity	NPC475590
0.6322	Remote Similarity	NPC99620
0.6322	Remote Similarity	NPC473852
0.6146	Remote Similarity	NPC125077
0.6061	Remote Similarity	NPC475219
0.6044	Remote Similarity	NPC77319
0.6044	Remote Similarity	NPC471351
0.6044	Remote Similarity	NPC471355
0.5978	Remote Similarity	NPC9499
0.5978	Remote Similarity	NPC471360
0.5978	Remote Similarity	NPC469751
0.5978	Remote Similarity	NPC471361
0.5978	Remote Similarity	NPC86159
0.5978	Remote Similarity	NPC469752
0.5978	Remote Similarity	NPC469754
0.5978	Remote Similarity	NPC70542
0.5934	Remote Similarity	NPC84949
0.5934	Remote Similarity	NPC480562
0.5934	Remote Similarity	NPC74945
0.5934	Remote Similarity	NPC31354
0.5934	Remote Similarity	NPC69576
0.5926	Remote Similarity	NPC189588
0.5914	Remote Similarity	NPC471354
0.5914	Remote Similarity	NPC27507
0.5843	Remote Similarity	NPC474418
0.5833	Remote Similarity	NPC236973
0.5824	Remote Similarity	NPC5311
0.5657	Remote Similarity	NPC486143
0.5657	Remote Similarity	NPC486142
0.5657	Remote Similarity	NPC486149
0.5652	Remote Similarity	NPC469750
0.5638	Remote Similarity	NPC471359
0.5638	Remote Similarity	NPC93883
0.5591	Remote Similarity	NPC199428
0.5591	Remote Similarity	NPC109448
0.5591	Remote Similarity	NPC76572
0.5591	Remote Similarity	NPC310341
0.5591	Remote Similarity	NPC193382
0.5529	Remote Similarity	NPC196471
0.5474	Remote Similarity	NPC484202
0.5472	Remote Similarity	NPC474908
0.5463	Remote Similarity	NPC474423
0.5455	Remote Similarity	NPC475556
0.5455	Remote Similarity	NPC311706
0.5417	Remote Similarity	NPC469753
0.5408	Remote Similarity	NPC30483
0.5408	Remote Similarity	NPC470897
0.5402	Remote Similarity	NPC475030
0.5392	Remote Similarity	NPC486146
0.5377	Remote Similarity	NPC475419
0.5376	Remote Similarity	NPC196429
0.5354	Remote Similarity	NPC292467
0.5333	Remote Similarity	NPC486144
0.5333	Remote Similarity	NPC486145
0.5333	Remote Similarity	NPC486147
0.5333	Remote Similarity	NPC486148
0.5319	Remote Similarity	NPC99080
0.5213	Remote Similarity	NPC484211
0.52	Remote Similarity	NPC32177
0.52	Remote Similarity	NPC469756
0.52	Remote Similarity	NPC275901
0.5158	Remote Similarity	NPC77299
0.5158	Remote Similarity	NPC480906
0.5155	Remote Similarity	NPC483822
0.5152	Remote Similarity	NPC103534
0.5152	Remote Similarity	NPC44899
0.5152	Remote Similarity	NPC304260
0.5152	Remote Similarity	NPC29639
0.5149	Remote Similarity	NPC188234
0.5149	Remote Similarity	NPC240070
0.5149	Remote Similarity	NPC608063
0.5104	Remote Similarity	NPC480914
0.5098	Remote Similarity	NPC231518
0.5098	Remote Similarity	NPC488944
0.5096	Remote Similarity	NPC329986
0.5096	Remote Similarity	NPC140092
0.505	Remote Similarity	NPC40749
0.5049	Remote Similarity	NPC486135
0.5049	Remote Similarity	NPC486137
0.5047	Remote Similarity	NPC329636
0.5046	Remote Similarity	NPC486134
0.5046	Remote Similarity	NPC486141

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC535419 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6396
0.1-0.2	2647
0.2-0.3	91
0.3-0.4	4
0.4-0.5	4
0.5-0.6	1
0.6-0.7	0
0.7-0.8	1
0.8-0.85	3
0.85-0.9	2
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD8296	Phase 4
0.8846	High Similarity	NPD8380	Approved
0.8718	High Similarity	NPD8335	Phase 4
0.8395	Intermediate Similarity	NPD8294	Phase 4
0.8353	Intermediate Similarity	NPD8378	Pre-clinical
0.8353	Intermediate Similarity	NPD8379	Approved
0.7033	Intermediate Similarity	NPD8377	Phase 4
0.5098	Remote Similarity	NPD8033	Approved

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